ABCC4

Summary

ABCC4 (ATP binding cassette subfamily C member 4 (PEL blood group), HGNC:55) is a protein-coding gene on chromosome 13q32.1, encoding ATP-binding cassette sub-family C member 4 (O15439). ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells.

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 10257 — RefSeq curated summary.

At a glance

• Gene–disease (curated): qualitative platelet defect (Moderate, ClinGen)
• GWAS associations: 19
• Clinical variants (ClinVar): 283 total — 49 pathogenic
• Druggable target: yes — 102 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_005845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:55
Approved symbol	ABCC4
Name	ATP binding cassette subfamily C member 4 (PEL blood group)
Location	13q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MRP4, EST170205, MOAT-B, MOATB
Ensembl gene	ENSG00000125257
Ensembl biotype	protein_coding
OMIM	605250
Entrez	10257

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000467685, ENST00000471041, ENST00000474158, ENST00000484109, ENST00000536256, ENST00000629385, ENST00000642524, ENST00000643051, ENST00000643556, ENST00000643816, ENST00000643842, ENST00000644471, ENST00000644880, ENST00000645237, ENST00000645532, ENST00000646439, ENST00000903573, ENST00000903574, ENST00000932202, ENST00000932203, ENST00000932204, ENST00000932205, ENST00000932206, ENST00000967420, ENST00000967421

RefSeq mRNA: 4 — MANE Select: NM_005845 NM_001105515, NM_001301829, NM_001301830, NM_005845

CCDS: CCDS45061, CCDS76643, CCDS86356, CCDS9474

Canonical transcript exons

ENST00000645237 — 31 exons

Exon	Start	End
ENSE00000853761	95166158	95166367
ENSE00000853762	95164378	95164518
ENSE00000853763	95163610	95163647
ENSE00000853764	95163122	95163216
ENSE00000853765	95161189	95161335
ENSE00000853766	95115922	95116001
ENSE00000853767	95083140	95083290
ENSE00000853768	95075432	95075551
ENSE00000853769	95074214	95074324
ENSE00000853770	95073204	95073304
ENSE00000853771	95071662	95071853
ENSE00000853772	95062704	95062859
ENSE00001101557	95043682	95043787
ENSE00001101565	95034605	95034739
ENSE00003466200	95194836	95194937
ENSE00003473956	95177997	95178091
ENSE00003497807	95207800	95207925
ENSE00003516540	95210692	95210781
ENSE00003516640	95234610	95234834
ENSE00003522147	95170532	95170628
ENSE00003525290	95209434	95209597
ENSE00003531806	95206532	95206781
ENSE00003536050	95188453	95188542
ENSE00003553727	95186701	95186892
ENSE00003556214	95053095	95053184
ENSE00003567037	95044266	95044438
ENSE00003578340	95247643	95247753
ENSE00003609340	95177707	95177793
ENSE00003689303	95246975	95247095
ENSE00003823291	95301241	95301451
ENSE00003823965	95019835	95021682

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5818 / max 422.7697, expressed in 1748 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137871	9.6929	1717
137872	2.2780	726
137874	0.9994	554
137870	0.2976	114
137873	0.2895	125
137865	0.0244	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	97.71	gold quality
secondary oocyte	CL:0000655	97.16	gold quality
buccal mucosa cell	CL:0002336	96.81	gold quality
oocyte	CL:0000023	95.63	gold quality
corpus epididymis	UBERON:0004359	95.42	gold quality
nephron tubule	UBERON:0001231	93.47	gold quality
mucosa of urinary bladder	UBERON:0001259	93.12	gold quality
choroid plexus epithelium	UBERON:0003911	91.26	gold quality
urinary bladder	UBERON:0001255	90.22	gold quality
epithelium of nasopharynx	UBERON:0001951	90.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.22	gold quality
stromal cell of endometrium	CL:0002255	87.55	gold quality
colonic mucosa	UBERON:0000317	87.39	gold quality
lower lobe of lung	UBERON:0008949	87.27	gold quality
kidney epithelium	UBERON:0004819	86.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.81	gold quality
prostate gland	UBERON:0002367	86.76	gold quality
renal glomerulus	UBERON:0000074	86.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.56	gold quality
metanephric glomerulus	UBERON:0004736	86.48	gold quality
cauda epididymis	UBERON:0004360	86.12	gold quality
colonic epithelium	UBERON:0000397	85.39	gold quality
ventricular zone	UBERON:0003053	84.13	gold quality
bronchial epithelial cell	CL:0002328	84.06	gold quality
metanephros cortex	UBERON:0010533	84.03	gold quality
cortex of kidney	UBERON:0001225	83.31	gold quality
monocyte	CL:0000576	83.28	gold quality
kidney	UBERON:0002113	83.22	gold quality
mononuclear cell	CL:0000842	82.92	gold quality
sigmoid colon	UBERON:0001159	82.83	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2758.01
E-GEOD-131882	yes	2298.71
E-MTAB-7381	yes	655.59
E-HCAD-25	yes	17.36
E-ANND-3	yes	15.68
E-MTAB-9067	yes	13.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, NFE2L2, NR1H4, NR1I3, TP53

miRNA regulators (miRDB)

143 targeting ABCC4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Literature-anchored findings (GeneRIF, showing 40)

• The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. (PMID:11856762)
• These findings indicate that a nucleotide transporter, such as MRP4, modulates the cellular response to ganciclovir and thus may influence not only the efficacy of antiviral therapy, but also prodrug-based gene therapy. (PMID:12105214)
• Impaired 2’,3’-dideoxy-3’-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11. (PMID:12133003)
• Steroid and bile acid conjugates are substrates of this protein. (PMID:12523936)
• MRP4 and MRP5 are low affinity cyclic nucleotide transporters that may at best function as overflow pumps, decreasing steep increases in cGMP levels under conditions where cGMP synthesis is strongly induced and phosphodiesterase activity is limiting (PMID:12637526)
• the affinity of MRP4 and MRP5 for nucleotide-based substrates is low. (PMID:12695538)
• MRP4 is not solely responsible for cisplatin resistance in small cell lung cancer (PMID:12792791)
• MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs (PMID:12835412)
• MRP4 can mediate the efflux of reduced glutathione from hepatocytes into blood by cotransport with monoanionic bile salts. (PMID:12883481)
• ABCC4 may play a role in the cellular extrusion of Phase II detoxification metabolites (PMID:14643890)
• ATP-dependent cGMP transport codistributed with MRP4 detection in platelet subcellular fractions, with highest activities in the dense granule and plasma membrane fractions; altered distribution of MRP4 was observed in Hermansky-Pudlak syndrome platelets (PMID:15297306)
• MRP4 exhibits substrate-stimulated ATP hydrolysis (PMID:15364914)
• MRP4 may have a role in MYCN oncogene amplification and in drug resistance in neuroblastoma (PMID:15827327)
• Plant flavonoids were able to reverse drug resistance in human cells transfected with ABCC4; direct inhibition of MRP4-mediated [3H]cGMP transport in inside-out vesicles prepared from human erythrocytes was observed. (PMID:16156793)
• In cholestatic conditions, ABCC4 may become a key pathway for efflux of bile acids from hepatocytes into blood. (PMID:16282361)
• Induction of MRP4 mediates resistance of Prostate cancer cells to nucleotide-based chemotherapeutic drugs. (PMID:17003774)
• ABCC4/Abcc4 and ABCG2/Abcg2 have roles in cGMP transport (PMID:17229149)
• cholestasis is one major determinant of human hepatic MRP4 expression (PMID:17404579)
• Inhibition of renal uptake (via OAT3) and efflux processes (via MRP2 and MRP4) explains the possible sites of drug-drug interaction for methotrexate with probenecid and some NSAIDs, including their glucuronides. (PMID:17578901)
• Results suggest that Bcrp and Mrp4 are partly involved in the luminal efflux of edaravone sulfate and edaravone glucuronide, respectively. (PMID:17682070)
• MRP4 protein levels were induced three-fold in primary biliary cirrhosis, whereas mRNA levels remained unchanged. (PMID:17696930)
• MRP-4 is induced by celecoxib in lung cancer cells (PMID:17878487)
• New comprehensive substrate-screening method for ABC transporters allowed the identification of 18 new substrates for MRP4. (PMID:17939016)
• The role of ABCC4 in the ATP-dependent efflux transport of leukotrienes B4 and C4 is shown in a number of different cell types. (PMID:17959747)
• Mrp4 knockout mice are more prone to CFTR-mediated secretory diarrhea. (PMID:18045536)
• Single nucleotide polymorphisms of ABCC4 were identified and selected nonsynonymous variants were functionally characterized. (PMID:18364470)
• Functional role of arginine 375 in transmembrane helix 6 of multidrug resistance protein 4 (MRP4/ABCC4) is reported. (PMID:18612080)
• MRP4/ABCC4 is an androgen-regulated gene important in the progression to prostate cancer and may be a potential drug target. (PMID:18615486)
• contributes to human DC migration toward the draining lymph nodes (PMID:18625884)
• ABCC4 regulates cAMP-dependent signaling pathways and controls human SMC proliferation. (PMID:18636120)
• The hepatic expression of multidrug-resistance protein 4 was enhanced in patients with untreated primary biliary cirrhosis at all stages. (PMID:18662272)
• Celecoxib upregulates MRP4 in colon cancer and results in lack of synergy with standard chemotherapy. (PMID:18690847)
• These data establish NHERF1 as a major determinant of MRP4 trafficking to apical membranes of mammalian kidney cells. (PMID:19073137)
• MRP3, MRP4, and MRP5 are upregulated in 5-fluorouracil-resistant cells, and MRP5 contributes to 5-FU resistance in pancreatic carcinoma cells. (PMID:19077464)
• Gaboxadol could be taken up into the kidney by hOAT1 followed by glucuronidation and efflux of the conjugate into urine via MRP4. (PMID:19082692)
• The existing model to explain increased PGE(2) in colorectal neoplasia should be modified to include the novel mechanism of coordinated up- and down-regulation of genes involved in PGE(2) transport. (PMID:19138942)
• mPGES-1 may be coupled to COX-1. ABCC4 up-regulation further supports the assumption of its involvement in prostanoid transport (PMID:19399588)
• Application of multivariate statistical procedures to identify transcription factors that correlate with MRP2, 3, and 4 mRNA in adult human livers. (PMID:19480556)
• Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. (PMID:19515727)
• The SNPs in ABCC4 might be applicable in predicting the risk of adverse drug reactions in patients receiving cyclophosphamide combination chemotherapy. (PMID:19696793)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcc4	ENSDARG00000058953
mus_musculus	Abcc4	ENSMUSG00000032849
rattus_norvegicus	Abcc4	ENSRNOG00000010064
drosophila_melanogaster	l(2)03659	FBGN0010549
drosophila_melanogaster	CG7627	FBGN0032026
drosophila_melanogaster	MRP	FBGN0032456
drosophila_melanogaster	CG9270	FBGN0032908
drosophila_melanogaster	CG10505	FBGN0034612
drosophila_melanogaster	Mrp5	FBGN0038740
drosophila_melanogaster	rdog	FBGN0039644
drosophila_melanogaster	CG11898	FBGN0039645
drosophila_melanogaster	CG31792	FBGN0051792
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477

Paralogs (11): CFTR (ENSG00000001626), ABCC8 (ENSG00000006071), ABCC2 (ENSG00000023839), ABCC9 (ENSG00000069431), ABCC6 (ENSG00000091262), ABCC1 (ENSG00000103222), ABCC3 (ENSG00000108846), ABCC5 (ENSG00000114770), ABCC11 (ENSG00000121270), ABCC10 (ENSG00000124574), ABCC12 (ENSG00000140798)

Protein

Protein identifiers

ATP-binding cassette sub-family C member 4 — O15439 (reviewed: O15439)

Alternative names: MRP/cMOAT-related ABC transporter, Multi-specific organic anion transporter B, Multidrug resistance-associated protein 4

All UniProt accessions (6): O15439, A0A2R8Y5Z3, A0A2R8Y6V8, A0A2R8YDC1, A0A2R8YDG7, Q8IWU1

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins. Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4. Mediates the cotransport of bile acids with reduced glutathione (GSH). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotic molecules. Confers resistance to anticancer agents such as methotrexate.

Subunit / interactions. Monomer. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); this interaction accelerates MRP4 internalization.

Subcellular location. Basolateral cell membrane. Apical cell membrane.

Tissue specificity. Widely expressed, with particularly high levels in prostate, but is barely detectable in liver. sinusoidal membrane of hepatocytes.

Post-translational modifications. N-glycosylated; leading to substrate-selective effects on its transport activity.

Activity regulation. GSH stimulates the transport of MRP4. Urate inhibits methotrexate transport but stimulates cGMP transport. Nonsteroidal anti-inflammatory drugs (NSAIDs) strongly suppress the transport of MRP4 substrates.

Domain organisation. The two ABC transmembrane type-1 domains are essential for substrates binding and transport. The two ABC transporter domains, also known as nucleotide-binding domains, are essential for ATP binding and hydrolysis.

Similarity. Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O15439-1	1	yes
O15439-2	2
O15439-3	3
O15439-4	4

RefSeq proteins (4): NP_001098985, NP_001288758, NP_001288759, NP_005836* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030240	ABCC4_TMD1	Domain
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR047083	ABCC4_TMD2	Domain
IPR050173	ABC_transporter_C-like	Family

Pfam: PF00005, PF00664

Enzyme classification (BRENDA):

• EC 7.6.2.2 — ABC-type xenobiotic transporter (BRENDA: 49 organisms, 716 substrates, 471 inhibitors, 280 Km, 31 kcat entries)
• EC 7.6.2.3 — ABC-type glutathione-S-conjugate transporter (BRENDA: 8 organisms, 145 substrates, 63 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

75 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0009–9	105
VERAPAMIL/IN	0.0006–0.0058	11
VINBLASTINE/IN	0.0002–0.1455	11
ESTRADIOL 17-BETA-D-GLUCURONIDE/IN	0.013–0.17	7
LEUKOTRIENE C4/IN	—	7
METHOTREXATE/IN	0.24–0.776	6
NICARDIPINE/IN	0.0004–0.0026	6
PROGESTERONE/IN	0.0038–0.0207	6
CYCLIC GUANOSINE MONOPHOSPHATE/IN	0.36–2	5
VERAPAMIL	0.0022–0.0115	5
ATP	0.0865–0.91	5
COLCHICINE/IN	0.037–0.72	4
FOLIC ACID/IN	0.13–0.26	4
PACLITAXEL/IN	0.0007–0.0009	4
RHODAMINE 123/IN	0.0118–0.0354	4

Catalyzed reactions (Rhea), 12 shown:

• urate(in) + ATP + H2O = urate(out) + ADP + phosphate + H(+) (RHEA:16461)
• an S-substituted glutathione(in) + ATP + H2O = an S-substituted glutathione(out) + ADP + phosphate + H(+) (RHEA:19121)
• leukotriene C4(in) + ATP + H2O = leukotriene C4(out) + ADP + phosphate + H(+) (RHEA:38963)
• 17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:60128)
• dehydroepiandrosterone 3-sulfate(in) + ATP + H2O = dehydroepiandrosterone 3-sulfate(out) + ADP + phosphate + H(+) (RHEA:61364)
• 3’,5’-cyclic AMP(in) + ATP + H2O = 3’,5’-cyclic AMP(out) + ADP + phosphate + H(+) (RHEA:66184)
• 3’,5’-cyclic GMP(in) + ATP + H2O = 3’,5’-cyclic GMP(out) + ADP + phosphate + H(+) (RHEA:66188)
• glycodeoxycholate(in) + glutathione(in) + ATP + H2O = glycodeoxycholate(out) + glutathione(out) + ADP + phosphate + H(+) (RHEA:66380)
• prostaglandin E2(in) + ATP + H2O = prostaglandin E2(out) + ADP + phosphate + H(+) (RHEA:66388)
• prostaglandin E1(in) + ATP + H2O = prostaglandin E1(out) + ADP + phosphate + H(+) (RHEA:66392)
• cholate(in) + glutathione(in) + ATP + H2O = cholate(out) + glutathione(out) + ADP + phosphate + H(+) (RHEA:66396)
• glycocholate(in) + glutathione(in) + ATP + H2O = glycocholate(out) + glutathione(out) + ADP + phosphate + H(+) (RHEA:66400)

UniProt features (204 total): helix 55, binding site 39, strand 30, sequence variant 23, topological domain 12, transmembrane region 12, turn 10, sequence conflict 5, domain 4, modified residue 4, splice variant 4, mutagenesis site 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
8XOK	ELECTRON MICROSCOPY	2.84
8ZBR	ELECTRON MICROSCOPY	2.92
8IZ9	ELECTRON MICROSCOPY	2.95
8ZBS	ELECTRON MICROSCOPY	2.96
9KRL	ELECTRON MICROSCOPY	2.99
8BJF	ELECTRON MICROSCOPY	3
9KRM	ELECTRON MICROSCOPY	3
8XOL	ELECTRON MICROSCOPY	3.02
8XOM	ELECTRON MICROSCOPY	3.05
8J3W	ELECTRON MICROSCOPY	3.07
8I4C	ELECTRON MICROSCOPY	3.08
8I4B	ELECTRON MICROSCOPY	3.13
8IZ8	ELECTRON MICROSCOPY	3.13
9KRN	ELECTRON MICROSCOPY	3.14
8J3Z	ELECTRON MICROSCOPY	3.17
8BWO	ELECTRON MICROSCOPY	3.2
8ZBU	ELECTRON MICROSCOPY	3.28
9KRK	ELECTRON MICROSCOPY	3.29
8I4A	ELECTRON MICROSCOPY	3.4
8IZA	ELECTRON MICROSCOPY	3.48
8BWP	ELECTRON MICROSCOPY	3.6
8IZ7	ELECTRON MICROSCOPY	3.8
8BWQ	ELECTRON MICROSCOPY	3.9
8ZBT	ELECTRON MICROSCOPY	3.9
8BWR	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15439-F1	83.42	0.46

Functional residue map

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

Ligand- & substrate-binding residues (39): 183; 284; 419; 448; 450; 451; 452; 452; 453; 480; 480; 533 …

Post-translational modifications (4): 646, 648, 664, 668

Mutagenesis-validated functional residues (2):

Position	Phenotype
746	does not affect plasma membrane localization; 1.5 fold increase in peg2 transport; does not affect estradiol 17-beta-d-g
754	does not affect plasma membrane localization; peg2 transport is decreased by 50%; does not affect estradiol 17-beta-d-gl

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-382556	ABC-family protein mediated transport
R-HSA-9748787	Azathioprine ADME
R-HSA-9753281	Paracetamol ADME
R-HSA-109582	Hemostasis
R-HSA-382551	Transport of small molecules
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-9748784	Drug ADME

MSigDB gene sets: 325 (showing top): LUCAS_HNF4A_TARGETS_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOCC_CELL_SURFACE, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT, KEGG_ABC_TRANSPORTERS

GO Biological Process (20): platelet degranulation (GO:0002576), obsolete L-tryptophan metabolic process (GO:0006568), xenobiotic metabolic process (GO:0006805), xenobiotic transmembrane transport (GO:0006855), bile acid and bile salt transport (GO:0015721), prostaglandin transport (GO:0015732), urate transport (GO:0015747), prostaglandin secretion (GO:0032310), kynurenic acid metabolic process (GO:0034275), transmembrane transport (GO:0055085), cilium assembly (GO:0060271), cAMP transport (GO:0070730), leukotriene transport (GO:0071716), export across plasma membrane (GO:0140115), transport across blood-brain barrier (GO:0150104), lipid transport (GO:0006869), response to xenobiotic stimulus (GO:0009410), glutathione transmembrane transport (GO:0034775), monoatomic anion transmembrane transport (GO:0098656), guanine nucleotide transmembrane transport (GO:1903790)

GO Molecular Function (19): guanine nucleotide transmembrane transporter activity (GO:0001409), ATP binding (GO:0005524), ABC-type xenobiotic transporter activity (GO:0008559), prostaglandin transmembrane transporter activity (GO:0015132), urate transmembrane transporter activity (GO:0015143), purine nucleotide transmembrane transporter activity (GO:0015216), ABC-type glutathione S-conjugate transporter activity (GO:0015431), ABC-type bile acid transporter activity (GO:0015432), efflux transmembrane transporter activity (GO:0015562), 15-hydroxyprostaglandin dehydrogenase (NAD+) activity (GO:0016404), ATP hydrolysis activity (GO:0016887), glutathione transmembrane transporter activity (GO:0034634), ATPase-coupled transmembrane transporter activity (GO:0042626), xenobiotic transmembrane transporter activity (GO:0042910), obsolete ATPase-coupled inorganic anion transmembrane transporter activity (GO:0043225), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (8): nucleolus (GO:0005730), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), platelet dense granule membrane (GO:0031088), external side of apical plasma membrane (GO:0098591)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Drug ADME	2
Response to elevated platelet cytosolic Ca2+	1
Transport of small molecules	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	3
ABC-type transporter activity	3
xenobiotic transport	2
icosanoid transport	2
prostaglandin transport	2
transport	2
sulfur compound transmembrane transporter activity	2
transmembrane transporter activity	2
ATP-dependent activity	2
plasma membrane region	2
regulated exocytosis	1
establishment of localization in cell	1
metabolic process	1
cellular response to xenobiotic stimulus	1
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
fatty acid transport	1
nitrogen compound transport	1
signal release	1
icosanoid secretion	1
lipid export from cell	1
monocarboxylic acid metabolic process	1
cellular process	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
purine ribonucleotide transport	1
adenine nucleotide transport	1
cyclic nucleotide transport	1
export from cell	1
vascular transport	1
lipid localization	1
response to chemical	1
glutathione transport	1

Protein interactions and networks

STRING

2060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC4	MRPS7	Q9Y2R9	948
ABCC4	SLC22A11	Q9NSA0	821
ABCC4	SLC22A7	Q9Y694	807
ABCC4	SLC22A8	Q8TCC7	797
ABCC4	SLC22A12	Q96S37	758
ABCC4	FABP6	P51161	730
ABCC4	SLCO1B1	Q9Y6L6	722
ABCC4	SLC22A6	Q4U2R8	722
ABCC4	SLC17A1	Q14916	718
ABCC4	SLCO1B3	Q9NPD5	714
ABCC4	NR1I2	O75469	714
ABCC4	SLCO2B1	O94956	713
ABCC4	CYP7A1	P22680	710
ABCC4	SLCO1A2	P46721	705
ABCC4	SLC22A9	Q8IVM8	703

IntAct

319 interactions, top by confidence:

A	B	Type	Score
MPP1	ABCC4	psi-mi:“MI:0407”(direct interaction)	0.780
MPP1	ABCC4	psi-mi:“MI:0915”(physical association)	0.780
ABCC4	MPP1	psi-mi:“MI:0915”(physical association)	0.780
MPP1	ABCC4	psi-mi:“MI:2364”(proximity)	0.780
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
SCRIB	ABCC4	psi-mi:“MI:0915”(physical association)	0.610
ABCC4	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.610
SCRIB	ABCC4	psi-mi:“MI:0407”(direct interaction)	0.610
ABCC4	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.590
ABCC4	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.590
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
REEP5	SCAMP1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
REEP5	PLSCR1	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530

BioGRID (118): SLC9A3R1 (Affinity Capture-Western), ABCC4 (Affinity Capture-Western), SLC9A3R1 (Reconstituted Complex), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1CZ63, B2RX12, B5X0E4, B8K1W2, E9Q236, F1M3J4, O15438, O15439, O35379, O70127, O80725, O88563, O95342, P06795, P08183, P21439, P21440, P21447, P21448, P21449, P23174, P33527, P43245, P91660, Q08201, Q2M3G0, Q42093, Q54JR2, Q54U44, Q5F364, Q6UR05, Q6Y306, Q7FB56, Q80WJ6, Q864R9, Q8CG09, Q8HXQ5, Q96J65, Q9C8G9, Q9C8H0

Diamond homologs: A0A0D1CZ63, A0A0U1LQE1, A0A1U8QTJ9, A2XCD4, A7KVC2, B2RX12, E9Q236, F1M3J4, F9X9V4, G4N2B5, J9VQH1, O15438, O15439, O15440, O31708, O35379, O60706, O70127, O88269, O88563, O95255, P0CE69, P14772, P16875, P16877, P21439, P21440, P32386, P33527, P38735, P39109, P53049, P70170, P82451, P91660, P9WEL8, Q07QX6, Q08201, Q09427, Q0VQP5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ABCC4	“up-regulates quantity”	“sphingosine 1-phosphate”	relocalization
ABCC4	“up-regulates activity”	BLOC-1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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	28.0×	6e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	26.7×	6e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	26.7×	6e-05
Long-term potentiation	5	23.3×	1e-04
Assembly and cell surface presentation of NMDA receptors	9	22.4×	4e-08
Neurexins and neuroligins	11	21.2×	1e-09
Protein-protein interactions at synapses	7	18.2×	1e-05
Formation of the dystrophin-glycoprotein complex (DGC)	6	18.2×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	42.9×	5e-13
receptor clustering	7	29.3×	1e-06
protein localization to synapse	5	25.7×	2e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	7	23.3×	6e-06
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	8.8×	4e-03
protein-containing complex assembly	10	7.6×	1e-04
cell-cell adhesion	9	6.1×	2e-03
chemical synaptic transmission	11	5.7×	4e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — ANGS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	0
Uncertain significance	148
Likely benign	19
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1341081	GRCh37/hg19 13q11-34(chr13:19436286-115107733)x3	Pathogenic
1341277	GRCh37/hg19 13q14.11-33.3(chr13:42504540-108206269)x3	Pathogenic
147510	GRCh38/hg38 13q31.3-33.3(chr13:93345058-109458154)x1	Pathogenic
148008	GRCh38/hg38 13q31.2-34(chr13:88937651-114327173)x3	Pathogenic
1527749	GRCh37/hg19 13q11-34(chr13:19436286-114981726)	Pathogenic
1527777	GRCh37/hg19 13q21.2-34(chr13:61424168-115107733)	Pathogenic
1527785	GRCh37/hg19 13q22.3-34(chr13:78514567-115107733)	Pathogenic
1527786	GRCh37/hg19 13q31.1-34(chr13:79370012-115107733)	Pathogenic
1527787	GRCh37/hg19 13q31.1-34(chr13:85037147-115107733)	Pathogenic
1527788	GRCh37/hg19 13q31.2-34(chr13:88073140-115107733)	Pathogenic
153403	GRCh38/hg38 13q31.1-34(chr13:83288131-114342258)x3	Pathogenic
154857	GRCh38/hg38 13q12.11-34(chr13:19671934-114340331)x3	Pathogenic
155395	GRCh38/hg38 13q11-34(chr13:18862146-114342258)x3	Pathogenic
1703573	GRCh37/hg19 13p13-q34(chr13:1-115169878)	Pathogenic
1707439	GRCh37/hg19 13q31.2-34(chr13:89490345-115062235)x3	Pathogenic
1807731	GRCh37/hg19 13q22.1-34(chr13:75268539-115107733)x3	Pathogenic
1808276	GRCh37/hg19 13q31.3-33.2(chr13:93535335-105788229)x1	Pathogenic
2446726	GRCh37/hg19 13q32.1-33.2(chr13:95700999-105271065)x3	Pathogenic
253405	GRCh37/hg19 13q12.11-34(chr13:19571503-115092569)x3	Pathogenic
2684705	GRCh37/hg19 13q22.1-34(chr13:73488238-115107733)x3	Pathogenic
2685475	GRCh37/hg19 13q31.1-34(chr13:82131211-115107733)x1	Pathogenic
3063279	GRCh37/hg19 13q14.2-32.2(chr13:49547974-98214905)x1	Pathogenic
3063280	GRCh37/hg19 13q21.31-33.1(chr13:64825656-103641349)x1	Pathogenic
3063294	GRCh37/hg19 13q31.1-34(chr13:82876219-115107733)x3	Pathogenic
3063309	GRCh37/hg19 13q31.1-34(chr13:84669397-115107733)x1	Pathogenic
395156	GRCh37/hg19 13q31.1-34(chr13:82221361-115092569)x3	Pathogenic
395197	GRCh37/hg19 13q31.1-33.1(chr13:81851091-102864674)x1	Pathogenic
395478	GRCh37/hg19 13q14.3-33.3(chr13:53551300-109850651)x1	Pathogenic
4076014	GRCh37/hg19 13q31.2-33.1(chr13:88690727-102272954)x1	Pathogenic
441662	GRCh37/hg19 13q21.33-34(chr13:71871468-115107733)x4	Pathogenic

SpliceAI

6662 predictions. Top by Δscore:

Variant	Effect	Δscore
13:95034599:GCTCA:G	donor_loss	1.0000
13:95034600:CTCAC:C	donor_loss	1.0000
13:95034601:TCA:T	donor_loss	1.0000
13:95034602:CA:C	donor_loss	1.0000
13:95034603:ACC:A	donor_loss	1.0000
13:95034604:C:CA	donor_loss	1.0000
13:95043676:ACTC:A	donor_loss	1.0000
13:95043677:CTCA:C	donor_loss	1.0000
13:95043678:TCACC:T	donor_loss	1.0000
13:95043679:CA:C	donor_loss	1.0000
13:95043680:A:AC	donor_gain	1.0000
13:95043680:A:C	donor_loss	1.0000
13:95043681:C:CC	donor_gain	1.0000
13:95043681:C:CG	donor_loss	1.0000
13:95043783:CAGTT:C	acceptor_gain	1.0000
13:95043784:AGTT:A	acceptor_gain	1.0000
13:95043784:AGTTC:A	acceptor_loss	1.0000
13:95043785:GTT:G	acceptor_gain	1.0000
13:95043786:TT:T	acceptor_gain	1.0000
13:95043786:TTC:T	acceptor_loss	1.0000
13:95043787:TCTG:T	acceptor_loss	1.0000
13:95043788:C:CC	acceptor_gain	1.0000
13:95043788:C:CG	acceptor_loss	1.0000
13:95043789:T:C	acceptor_loss	1.0000
13:95044257:G:C	donor_gain	1.0000
13:95062885:T:TC	acceptor_gain	1.0000
13:95073309:G:C	acceptor_gain	1.0000
13:95115880:T:TA	donor_gain	1.0000
13:95116002:C:CC	acceptor_gain	1.0000
13:95161854:T:C	acceptor_gain	1.0000

AlphaMissense

8633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:95044344:A:G	L1184P	0.999
13:95044361:A:C	S1178R	0.999
13:95044361:A:T	S1178R	0.999
13:95044363:T:G	S1178R	0.999
13:95044357:C:G	G1180R	0.998
13:95044357:C:T	G1180R	0.998
13:95062828:T:A	K1081I	0.998
13:95206637:G:C	F352L	0.998
13:95206637:G:T	F352L	0.998
13:95206639:A:G	F352L	0.998
13:95044272:T:C	D1208G	0.997
13:95044335:A:G	L1187P	0.997
13:95044346:T:A	Q1183H	0.997
13:95044346:T:G	Q1183H	0.997
13:95044356:C:T	G1180E	0.997
13:95053147:A:G	L1135P	0.997
13:95062711:A:T	I1120K	0.997
13:95062728:C:A	R1114S	0.997
13:95062728:C:G	R1114S	0.997
13:95062729:C:A	R1114M	0.997
13:95062729:C:G	R1114T	0.997
13:95075544:A:C	S898R	0.997
13:95075544:A:T	S898R	0.997
13:95075546:T:G	S898R	0.997
13:95083156:C:A	K890N	0.997
13:95083156:C:G	K890N	0.997
13:95178029:A:C	S536R	0.997
13:95178029:A:T	S536R	0.997
13:95178031:T:G	S536R	0.997
13:95043716:C:G	R1234T	0.996

dbSNP variants (sampled 300 via entrez): RS1000004254 (13:95279739 C>A,G,T), RS1000007264 (13:95105508 T>A), RS1000028039 (13:95043818 T>C), RS1000039740 (13:95245617 T>A,C), RS1000040774 (13:95276003 T>G), RS1000042746 (13:95063201 A>G), RS1000054411 (13:95056899 A>G), RS1000055681 (13:95231669 G>A), RS1000069091 (13:95282499 G>A), RS1000086022 (13:95205004 G>A,T), RS1000087874 (13:95110925 G>A), RS1000093379 (13:95245912 G>A), RS1000098688 (13:95167464 G>C), RS1000119681 (13:95152011 C>A,T), RS1000132115 (13:95191230 G>C)

Disease associations

OMIM: gene MIM:605250 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
qualitative platelet defect	Moderate	AR

Mondo (3): prostate cancer (MONDO:0008315), trisomy 13 (MONDO:0018068), primary ovarian failure (MONDO:0005387)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Trisomy 13 syndrome (Orphanet:3378), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000079_9	Breast cancer	2.000000e-06
GCST000785_13	Longevity	1.000000e-06
GCST001337_40	Platelet count	7.000000e-12
GCST001901_1	Response to irinotecan and platinum-based chemotherapy in non-small-cell lung cancer	2.000000e-07
GCST002371_4	Parent of origin effect on language impairment (paternal)	6.000000e-06
GCST002724_19	Airway responsiveness in chronic obstructive pulmonary disease	7.000000e-06
GCST004603_128	Platelet count	9.000000e-22
GCST004603_129	Platelet count	9.000000e-30
GCST004607_91	Plateletcrit	2.000000e-28
GCST004607_92	Plateletcrit	3.000000e-30
GCST005991_32	Platelet count	7.000000e-36
GCST008388_1	Acute post-radiotherapy pain in breast cancer	5.000000e-06
GCST010397_89	Gut microbiota (bacterial taxa, rank normal transformation method)	5.000000e-09
GCST012020_334	Serum metabolite levels	6.000000e-32
GCST012124_1	Postherpetic neuralgia	2.000000e-07
GCST90002400_122	Plateletcrit	2.000000e-101
GCST90002400_123	Plateletcrit	4.000000e-38
GCST90002402_217	Platelet count	8.000000e-93
GCST90002402_218	Platelet count	1.000000e-28

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0006897	airway responsiveness measurement
EFO:0007985	platelet crit
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1743128 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

102 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 371,334 (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
CHEMBL1010	CEFOTAXIME SODIUM	4	4,928
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1095930	CEFUROXIME AXETIL	4	237
CHEMBL1096	AMLEXANOX	4	4,195
CHEMBL1096885	VALRUBICIN	4	41,463
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1131	ACITRETIN	4	13,259
CHEMBL1136	TELITHROMYCIN	4	15,927
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1164729	FEBUXOSTAT	4	3,499
CHEMBL1200523	CEFAZOLIN SODIUM	4	9,725
CHEMBL1200561	DOXAZOSIN MESYLATE	4	11,917
CHEMBL1200621	GEMIFLOXACIN MESYLATE	4	884
CHEMBL1200692	OLMESARTAN MEDOXOMIL	4	17,268
CHEMBL1200799	TRAVOPROST	4	9,398
CHEMBL1200896	DINOPROST TROMETHAMINE	4	1,764
CHEMBL1201124	KETOROLAC TROMETHAMINE	4	18,700
CHEMBL1201182	TEMSIROLIMUS	4	25,195
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL1272	REPAGLINIDE	4
CHEMBL1292	CLOFAZIMINE	4
CHEMBL1294	QUINIDINE	4
CHEMBL1316	CARPROFEN	4
CHEMBL1324	TOLCAPONE	4
CHEMBL1370	BUDESONIDE	4
CHEMBL1456	MYCOPHENOLATE MOFETIL	4
CHEMBL1481	GLIMEPIRIDE	4
CHEMBL1484	NICARDIPINE	4
CHEMBL1509	DROSPIRENONE	4

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

PharmGKB clinical annotations

18 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1059751	Toxicity	3	tenofovir	HIV infectious disease
rs11568658	Efficacy	3	latanoprost	Open-angle glaucoma
rs11568658	Toxicity	3	valganciclovir	Kidney Transplantation
rs11568695	Other	3	zidovudine	HIV infectious disease
rs1678387	Toxicity	3	Bisphosphonates	Osteonecrosis
rs16950650	Efficacy	3	cisplatin;irinotecan	Small cell carcinoma
rs17268282	Efficacy	3	furosemide	Heart Failure
rs1751034	Metabolism/PK	4	tenofovir	HIV infectious disease
rs3742106	Toxicity	3	tenofovir disoproxil fumarate	HIV infectious disease;Nephrotoxicity
rs3742106	Metabolism/PK	3	tenofovir	HIV infectious disease
rs3765534	Toxicity	3	azathioprine;mercaptopurine	Inflammatory Bowel Diseases
rs7317112	Toxicity	3	methotrexate	Acute lymphoblastic leukemia
rs7317112	Toxicity	3	glucarpidase	Nephrotoxicity
rs899494	Toxicity	4	tenofovir	Drug Toxicity;HIV infectious disease
rs9516519	Toxicity	3	methotrexate	Burkitt Lymphoma
rs9561765	Efficacy	3	imatinib	Gastrointestinal Stromal Tumors
rs9561778	Toxicity	3	cyclophosphamide	Breast Neoplasms;Drug Toxicity
rs9561778	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms;Neoplasms

PharmGKB variants

34 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs868853	ABCC4		0.00	0
rs899494	ABCC4	4	-1.50	1	tenofovir
rs1059751	ABCC4	3	2.25	1	tenofovir
rs1557070	ABCC4		0.00	0
rs1678387	ABCC4	3	0.00	1	Bisphosphonates
rs1751034	ABCC4	4	-0.50	1	tenofovir
rs2274405	ABCC4		0.00	0
rs2274406	ABCC4		0.00	0
rs2274407	ABCC4		0.00	0
rs3742106	ABCC4	3	3.50	2	tenofovir disoproxil fumarate;tenofovir
rs3765534	ABCC4	3	2.50	1	azathioprine;mercaptopurine
rs4773866	ABCC4		0.00	0
rs7317112	ABCC4	3	2.50	2	methotrexate;glucarpidase
rs9516519	ABCC4	3	4.00	1	methotrexate
rs9556455	ABCC4		0.00	0
rs9561765	ABCC4	3	2.25	1	imatinib
rs9561778	ABCC4	3	7.75	2	cyclophosphamide;cyclophosphamide;doxorubicin;fluorouracil
rs11568655	ABCC4		0.00	0
rs11568658	ABCC4	3	2.75	2	latanoprost;valganciclovir
rs11568668	ABCC4		0.00	0
rs11568695	ABCC4	3	0.12	1	zidovudine
rs16950650	ABCC4	3	0.00	1	cisplatin;irinotecan
rs17268122	ABCC4		0.00	0
rs17268282	ABCC4	3	1.38	1	furosemide
rs146708960	ABCC4		0.00	0
rs4771904	ABCC4		0.00	0
rs1678396	ABCC4		0.00	0
rs4148472	ABCC4		0.00	0
rs7322318	ABCC4		0.00	0
rs200858900	ABCC4		0.00	0
rs11568644	ABCC4		0.00	0
rs11568681	ABCC4		0.00	0
rs142211148	ABCC4		0.00	0
rs11568684	ABCC4		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCC subfamily

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

Ligand	Action	Affinity	Parameter
estradiol disulfate	Inhibition	6.7	pIC50

ChEMBL bioactivities

43 potent at pChembl≥5 of 136 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	ESTRADIOL DISULFATE
6.00	IC50	1000	nM	TRANILAST
5.82	IC50	1500	nM	SULFASALAZINE
5.72	IC50	1900	nM	FEBUXOSTAT
5.72	IC50	1900	nM	CLOPROSTENOL SODIUM
5.70	IC50	2000	nM	DIPYRIDAMOLE
5.70	IC50	2000	nM	ESTRADIOL DISULFATE
5.66	IC50	2200	nM	AMLEXANOX
5.64	IC50	2300	nM	ALPROSTADIL
5.57	IC50	2700	nM	PRANLUKAST
5.57	IC50	2700	nM	CHEMBL4097197
5.57	IC50	2700	nM	KETOROLAC TROMETHAMINE
5.52	IC50	3000	nM	PRASTERONE SULFURIC ACID
5.52	IC50	3000	nM	CARPROFEN
5.40	Ki	4000	nM	RIMONABANT
5.34	IC50	4600	nM	GEFITINIB
5.29	IC50	5100	nM	RUBITECAN
5.24	IC50	5800	nM	INDOMETHACIN
5.22	IC50	6000	nM	MK-571
5.21	IC50	6200	nM	BMS-986020
5.20	IC50	6300	nM	GLIQUIDONE
5.20	IC50	6310	nM	BMS-986020
5.19	IC50	6500	nM	EPALRESTAT
5.19	IC50	6400	nM	DIACEREIN
5.17	IC50	6800	nM	ENTACAPONE
5.16	Ki	7000	nM	CHEMBL364300
5.15	IC50	7100	nM	TELITHROMYCIN
5.15	IC50	7100	nM	DINOPROST TROMETHAMINE
5.13	IC50	7400	nM	CAMPTOTHECIN
5.13	IC50	7430	nM	AMSACRINE
5.12	IC50	7500	nM	CHEMBL4085102
5.10	IC50	8000	nM	DOXAZOSIN MESYLATE
5.09	IC50	8100	nM	PAZOPANIB
5.09	IC50	8080	nM	CHEMBL4063475
5.09	IC50	8200	nM	FELBINAC
5.08	IC50	8300	nM	DIPYRIDAMOLE
5.02	IC50	9600	nM	TUBOCURARINE
5.01	IC50	9800	nM	PRANOPROFEN
5.00	IC50	1e+04	nM	TREQUINSIN
5.00	IC50	1e+04	nM	MK-571
5.00	IC50	1e+04	nM	CHEMBL2074644
5.00	IC50	1e+04	nM	CHEMBL260315
5.00	IC50	1e+04	nM	CHEMBL2074584

PubChem BioAssay actives

42 with measured affinity, of 784 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
[(8R,9S,13S,14S,17S)-13-methyl-3-sulfooxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] hydrogen sulfate	678790: TP_TRANSPORTER: inhibition of DHEAS in membrane vesicles from MRP4-expressing Sf9 cells	ic50	0.2000	uM
2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]benzoic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	1.0000	uM
2-hydroxy-5-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	1.5000	uM
Febuxostat	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	1.9000	uM
sodium (Z)-7-[2-[(E)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]hept-5-enoate	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	1.9000	uM
Dipyridamole	678791: TP_TRANSPORTER: inhibition of 9-(2-phosphonomethoxyethyl)adenine(PMEA) efflux (PMEA: 1 uM) in MRP4-expressing HEK293 cells	ic50	2.0000	uM
2-amino-5-oxo-7-propan-2-ylchromeno[2,3-b]pyridine-3-carboxylic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	2.2000	uM
Alprostadil	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	2.3000	uM
N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]-4-(4-phenylbutoxy)benzamide	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	2.7000	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine;methanesulfonic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	2.7000	uM
Ketorolac Tromethamine	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	2.7000	uM
[(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] hydrogen sulfate	681920: TP_TRANSPORTER: inhibition of E217betaG uptake in membrane vesicles from MRP4-expressing Sf9 cells	ic50	3.0000	uM
Carprofen	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	3.0000	uM
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide	1217133: Noncompetitive inhibition of MRP4-mediated E2-17betaG transport in human MRP4 expressing HEK293 cells by Dixon plot	ki	4.0000	uM
Gefitinib	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	4.6000	uM
(19S)-19-ethyl-19-hydroxy-8-nitro-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	5.1000	uM
Indomethacin	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	5.8000	uM
3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	6.0000	uM
1-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid	1813455: Inhibition of MRP4 (unknown origin)	ic50	6.2000	uM
1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethyl]phenyl]sulfonylurea	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	6.3000	uM
4,5-diacetyloxy-9,10-dioxoanthracene-2-carboxylic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	6.4000	uM
2-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	6.5000	uM
Entacapone	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	6.8000	uM
5-(4-chlorophenyl)-N-[ethyl(methyl)sulfamoyl]-N’-methyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide	1217133: Noncompetitive inhibition of MRP4-mediated E2-17betaG transport in human MRP4 expressing HEK293 cells by Dixon plot	ki	7.0000	uM
Telithromycin	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	7.1000	uM
Dinoprost Tromethamine	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	7.1000	uM
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	7.4000	uM
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	7.4300	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-5-amino-5-oxopentanoyl]amino]-5-amino-5-oxopentanoyl]amino]-5-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-oxopentanoic acid;acetic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	7.5000	uM
Doxazosin Mesylate	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	8.0000	uM
(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;hydrate	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	8.0800	uM
Pazopanib	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	8.1000	uM
2-(4-phenylphenyl)acetic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	8.2000	uM
Tubocurarine	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	9.6000	uM
2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoic acid	1473741: Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	ic50	9.8000	uM
(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-sulfooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	681389: TP_TRANSPORTER: inhibition of E217betaG uptake in membrane vesicles from MRP4-expressing HEK-293 cells	ic50	10.0000	uM
9,10-dimethoxy-3-methyl-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one	678791: TP_TRANSPORTER: inhibition of 9-(2-phosphonomethoxyethyl)adenine(PMEA) efflux (PMEA: 1 uM) in MRP4-expressing HEK293 cells	ic50	10.0000	uM
2-[[(4R)-4-[(3R,5R,8R,9S,10S,13R,14S)-10,13-dimethyl-3-sulfooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	681389: TP_TRANSPORTER: inhibition of E217betaG uptake in membrane vesicles from MRP4-expressing HEK-293 cells	ic50	10.0000	uM
2-[[(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-sulfooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]acetic acid	681389: TP_TRANSPORTER: inhibition of E217betaG uptake in membrane vesicles from MRP4-expressing HEK-293 cells	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	6
Methotrexate	increases export, decreases expression, affects transport, decreases reaction, increases transport (+2 more)	6
Valproic Acid	decreases reaction, decreases activity, affects cotreatment, increases expression, decreases expression	6
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression	5
Acetaminophen	increases expression, affects activity, increases transport, affects cotreatment	4
Cacodylic Acid	affects export, affects cotreatment, increases abundance, increases reaction, increases export (+1 more)	4
Cyclosporine	increases expression, affects expression	4
methylselenic acid	decreases expression, decreases reaction, affects expression	3
arsenite	affects cotreatment, increases abundance, increases reaction, affects binding, increases expression (+1 more)	3
Adenosine Triphosphate	affects reaction, affects binding, increases hydrolysis, affects activity, increases transport (+2 more)	3
Air Pollutants	affects expression, increases abundance, decreases expression, affects cotreatment	3
Arsenic	increases abundance, increases transport, affects methylation, increases expression, increases reaction (+1 more)	3
Chenodeoxycholic Acid	increases reaction, decreases expression, affects cotreatment, increases expression, affects binding (+1 more)	3
Cisplatin	increases expression, decreases response to substance, decreases expression	3
Estradiol	affects cotreatment, increases expression	3
Glutathione	affects transport, affects binding, increases export, increases reaction	3
Quercetin	decreases reaction, increases activity, affects reaction, increases reaction, decreases expression (+3 more)	3
Tretinoin	increases expression, decreases expression	3
Zidovudine	increases export, increases expression, affects abundance	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
diethyl phthalate	affects cotreatment, decreases expression, decreases reaction, increases expression	2
8-azidoadenosine 5’-triphosphate	decreases reaction, affects binding	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
estradiol-17 beta-glucuronide	affects export, increases export, increases transport	2
oltipraz	increases reaction, increases transport, increases expression	2
butylbenzyl phthalate	increases expression, affects cotreatment, decreases expression, decreases reaction	2
mercuric bromide	decreases expression, affects cotreatment	2
verlukast	affects export, decreases reaction, decreases response to substance, increases activity, decreases activity	2
TAK-875	decreases activity, decreases reaction, increases transport	2
Celecoxib	decreases activity, increases expression	2

ChEMBL screening assays

97 unique, capped per target: 71 functional, 21 admet, 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743162	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, MRP4	Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL2075982	Functional	TP_TRANSPORTER: uptake in membrane vesicles from MRP4-expressing Sf9 cells	Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. — Cancer Res
CHEMBL4002488	Binding	Inhibition of MRP4 in 7 mW/cm'2 irradiated human M14 cells assessed as nitration of tyrosine in MRP4 at 5 uM measured after 20 mins by immunoblotting	Light-Regulated NO Release as a Novel Strategy To Overcome Doxorubicin Multidrug Resistance. — ACS Med Chem Lett

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B6A1	C2BBe1 MRP4 KO	Cancer cell line	Male
CVCL_B6A4	C2BBe1 MRP3/MRP4 KO	Cancer cell line	Male
CVCL_B6AH	HepaRG MRP2/MRP4 KO	Cancer cell line	Female
CVCL_B6AJ	HepaRG MRP4 KO	Cancer cell line	Female
CVCL_D1V1	Abcam A-549 ABCC4 KO	Cancer cell line	Male
CVCL_D1ZP	Abcam HCT 116 ABCC4 KO	Cancer cell line	Male
CVCL_SB06	HAP1 ABCC4 (-) 1	Cancer cell line	Male
CVCL_XK89	HAP1 ABCC4 (-) 2	Cancer cell line	Male
CVCL_XK90	HAP1 ABCC4 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
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NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
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NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
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NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
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NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
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NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
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