ABCC2

Summary

ABCC2 (ATP binding cassette subfamily C member 2, HGNC:53) is a protein-coding gene on chromosome 10q24.2, encoding ATP-binding cassette sub-family C member 2 (Q92887). ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes.

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 protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia.

Source: NCBI Gene 1244 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Dubin-Johnson syndrome (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 1,313 total — 134 pathogenic, 52 likely-pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:53
Approved symbol	ABCC2
Name	ATP binding cassette subfamily C member 2
Location	10q24.2
Locus type	gene with protein product
Status	Approved
Aliases	DJS, MRP2, cMRP
Ensembl gene	ENSG00000023839
Ensembl biotype	protein_coding
OMIM	601107
Entrez	1244

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000370434, ENST00000496621, ENST00000647814, ENST00000647836, ENST00000648324, ENST00000648523, ENST00000648689, ENST00000649459, ENST00000649493, ENST00000649932

RefSeq mRNA: 1 — MANE Select: NM_000392 NM_000392

CCDS: CCDS7484

Canonical transcript exons

ENST00000647814 — 32 exons

Exon	Start	End
ENSE00000502459	99800386	99800563
ENSE00000502462	99807384	99807521
ENSE00000719698	99784608	99784781
ENSE00000719702	99792234	99792359
ENSE00000719714	99794413	99794468
ENSE00000719718	99797097	99797331
ENSE00000719721	99799207	99799370
ENSE00000719753	99804019	99804273
ENSE00000719768	99805382	99805447
ENSE00000719782	99808083	99808229
ENSE00000719787	99810134	99810218
ENSE00000719801	99811536	99811602
ENSE00000719839	99813018	99813144
ENSE00000719856	99817308	99817484
ENSE00000719906	99818790	99818957
ENSE00000719916	99819089	99819269
ENSE00000719930	99830307	99830433
ENSE00000719954	99830716	99830851
ENSE00000719985	99831611	99831830
ENSE00000720031	99831977	99832131
ENSE00000720045	99834380	99834535
ENSE00000720151	99843799	99843900
ENSE00000720167	99844322	99844465
ENSE00000720218	99845624	99845782
ENSE00000720232	99846961	99847127
ENSE00000720285	99850602	99850796
ENSE00001121971	99841967	99842093
ENSE00001121978	99836091	99836290
ENSE00003519551	99793551	99793685
ENSE00003599605	99793892	99793999
ENSE00003833855	99782640	99782877
ENSE00003841175	99851502	99852594

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 97.47.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1050 / max 274.9904, expressed in 282 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106505	1.1699	100
106501	1.0755	141
106504	0.2929	84
106508	0.1736	60
106503	0.1718	65
106506	0.1387	46
106502	0.0431	25
106507	0.0395	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.47	gold quality
liver	UBERON:0002107	93.84	gold quality
jejunal mucosa	UBERON:0000399	92.98	gold quality
gall bladder	UBERON:0002110	90.00	gold quality
duodenum	UBERON:0002114	89.62	gold quality
adult mammalian kidney	UBERON:0000082	80.63	gold quality
ileal mucosa	UBERON:0000331	78.38	gold quality
small intestine	UBERON:0002108	77.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.19	gold quality
tibial nerve	UBERON:0001323	77.06	gold quality
jejunum	UBERON:0002115	76.46	gold quality
metanephros cortex	UBERON:0010533	74.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.05	gold quality
kidney	UBERON:0002113	74.01	gold quality
sural nerve	UBERON:0015488	71.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.96	gold quality
diaphragm	UBERON:0001103	69.93	gold quality
cortex of kidney	UBERON:0001225	69.25	gold quality
mucosa of stomach	UBERON:0001199	68.05	gold quality
popliteal artery	UBERON:0002250	67.41	gold quality
tibial artery	UBERON:0007610	67.40	gold quality
gastrocnemius	UBERON:0001388	67.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	67.04	gold quality
muscle of leg	UBERON:0001383	66.79	gold quality
omental fat pad	UBERON:0010414	66.36	gold quality
nephron tubule	UBERON:0001231	66.34	silver quality
peritoneum	UBERON:0002358	66.29	gold quality
tongue squamous epithelium	UBERON:0006919	66.25	gold quality
granulocyte	CL:0000094	65.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	343.20
E-MTAB-6819	yes	156.38
E-ANND-3	yes	6.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ABCB1	Repression

Upstream regulators (CollecTRI, top): AHR, CEBPB, CEBPG, ESR1, FOXA2, FOXM1, FOXO1, GATA3, HNF1A, HNF1B, HNF4A, IRF3, NFE2L2, NR1H3, NR1H4, NR1I2, NR1I3, NR3C1, ONECUT1, RARA, RXRA, SP1, TP53, YBX1

miRNA regulators (miRDB)

57 targeting ABCC2, 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-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-376A-3P	99.06	69.17	1128

Literature-anchored findings (GeneRIF, showing 40)

• Two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome. (PMID:11477083)
• No change in cMOAT mRNA expression was detected in non-HTLV-1 Tax producing ATL cell lines following transfection with HTLV-1 Tax. (PMID:11937269)
• structural requirements for apical sorting (PMID:11952788)
• Impaired protein maturation followed by proteasomal degradation of inactive MRP2I1173F explain the deficient hepatobiliary elimination observed in this group of Dubin-Johnson syndrome patients. (PMID:12388192)
• mutation in MRP2 causes deficient maturation and impaired sorting in cells in Dubin-Johnson syndrome (PMID:12395335)
• RNA expression of this protein in breast cancer correlates with response to chemotherapy. (PMID:12576456)
• The role of multidrug resistance proteins MRP1, MRP2 and MRP3 in cellular folate homeostasis. (PMID:12628490)
• study of the interactions of drugs, organic anions, and bile acids with MRP2 substrates shows MRP2 contains two similar but nonidentical ligand binding sites: a substrate transport site and a site that regulates the affinity of the transport site (PMID:12702717)
• MRP2 active transport of estradiol-17-beta-d-glucuronide and MRP2 ATPase characteristics in isolated, inside-out membrane vesicles (PMID:12704183)
• MRP1 and MRP2 were expressed in peripheral blood cells, with more than sevenfold higher MRP1 expression. The MRP2 mRNA expression was highest in CD4+ cells, followed by CD8+ > CD56+ > CD19+ cells. (PMID:12890151)
• Homozygous mutation Arg768Trp in the ABC-transporter encoding gene multidrug-resistance-associated-protein 2 causes Dubin-Johnson syndrome (PMID:12942343)
• Disrupted localization of radixin and MRP2 supports the concept that radixin contributes to the canalicular localization of MRP2. (PMID:14568249)
• Cholestasis promotes down-regulation of MRP2 expression in the duodenum of humans. (PMID:15057744)
• ABCC2 promoter polymorphism is not a determinant of the risk of spinal dysraphism. (PMID:15211708)
• “MRP2(multidrug resistance-associated protein 2) is associated with active drug efflux and may influence oral bioavailability of common classes of drugs. (PMID:15848949)
• Dysfunction or loss of the multidrug resistance protein 2 (MRP2) is the molecular basis of Dubin-Johnson syndrome (DJS). (PMID:15870973)
• The major canalicular transporter genes are expressed at mid-gestational stage during human fetal development. (PMID:15922475)
• ABCB1, ABCC1, ABCC2, and ABCG2 haplotypes influence response to nelfinavir (PMID:16041239)
• nuclear factor, erythroid derived 2, like 2 appears to regulate Mrp2 gene expression via an antioxidant-response element element located at the proximal region of its promoter in response to exposure to xenobiotics (PMID:16426233)
• enhanced expression of MRP2 and lower expression of AQP3 are responsible for lower arsenic accumulation in arsenic-resistant cells (PMID:16672223)
• ABCC2 genotype modulates the expression in the unaffected renal cortex of renal cell cancer patients (PMID:16788565)
• The mRNA induction of MDR1, MRP1, MRP2 and MRP3 by rifampicin (Rif), dexamethasone (Dex) and omeprazole (Ome) was investigated in primary cultures of cryopreserved human and rat hepatocytes. (PMID:16946557)
• The ABCC2 c.1446C>G SNP is associated with reduced systemic exposure to pravastatin as a consequence of increased MRP2 expression. (PMID:17047488)
• the C-24T SNP of MRP2 is associated with a lower oral clearance of mycophenolic acid in steady-state conditions (PMID:17060857)
• ABCC2 polymorphism contributes to variability of methotrexate kinetics. (PMID:17112803)
• The expression of ABCC2 in nuclear membranes in human tissues is specific for poorly differentiated cells including stem cells. (PMID:17145840)
• Human corneal epithelium expresses the multidrug resistance associated protein ABCC2. ABCC2 contributes to drug efflux from the eye. (PMID:17156953)
• Allelic variants of UGT2B7, CYP2C8, and ABCC2, which may predispose to the formation and accumulation of reactive diclofenac metabolites are associated with diclofenac hepatotoxicity (PMID:17241877)
• I1173F causing DJS in Iranian Jews occurred after the separation of Iranian Jews from Moroccan Jews 2000-2600 years ago, while A244V causing FVII deficiency in Iranian and Moroccan Jews occurred prior to the divergence of these two populations. (PMID:17287630)
• Rotor-type hyperbilirubinaemia is not an allelic variant of ABCC2 deficiency. (PMID:17403188)
• Results show that the molecular model of ABCC2 agreed well with experimentally determined ABCC2-ligand interactions and the interaction of ABCC2 with quercetin glucuronides is dependent on the position and nature of substitution. (PMID:17478601)
• Mrp2 and Mrp3 provide alternative routes for the excretion of a glucuronidated substrate from the liver in vivo. (PMID:17485564)
• MRP1-Pro(1150), MRP2-Pro(1158), and MRP3-Pro(1147) in the cytoplasmic loop 7 differ in their influence on substrate specificity but share a common role in the nucleotide interactions at nucleotide binding domain 2 of these transporters. (PMID:17494643)
• 12 polymorphisms and mutations were found in the MRP2 gene in a Korean population. (PMID:17502832)
• 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)
• neither MRP1 nor MRP2 appears to have a role in response to cisplatin-based chemotherapy in resected non-small cell lung cancer (PMID:17606722)
• Report disturbed colocalization of multidrug resistance protein 2 and radixin in human cholestatic liver diseases. (PMID:17725603)
• Radixin and ezrin play similar roles in the apical membrane localization of ABCC2 (MRP2) and their expression level and subcellular distribution are important factors in the regulation of ABCC2 (MRP2) at the post-transcriptional level. (PMID:17825285)
• This study showed that manipulation of drug efflux transporters may be a useful strategy for increasing the intracellular concentration and thereby enhancing the clinical efficacy of lopinavir. (PMID:17890284)
• we observed that haplotype frequency of the ABCC2 gene in intrahepatic cholestasis of pregnancy patients significantly differed from controls (PMID:17997497)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Abcc2	ENSMUSG00000025194
rattus_norvegicus	Abcc2	ENSRNOG00000046727
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	CG31793	FBGN0051793
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477
caenorhabditis_elegans		WBGENE00003413

Paralogs (11): CFTR (ENSG00000001626), ABCC8 (ENSG00000006071), ABCC9 (ENSG00000069431), ABCC6 (ENSG00000091262), ABCC1 (ENSG00000103222), ABCC3 (ENSG00000108846), ABCC5 (ENSG00000114770), ABCC11 (ENSG00000121270), ABCC10 (ENSG00000124574), ABCC4 (ENSG00000125257), ABCC12 (ENSG00000140798)

Protein

Protein identifiers

ATP-binding cassette sub-family C member 2 — Q92887 (reviewed: Q92887)

Alternative names: Canalicular multidrug resistance protein, Canalicular multispecific organic anion transporter 1, Multidrug resistance-associated protein 2

All UniProt accessions (5): A0A3B3IRU4, A0A3B3IRZ2, A0A3B3IS94, A0A3B3ITG8, Q92887

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates. Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification. Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4. Transports sulfated bile salt such as taurolithocholate sulfate. Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors. Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed by polarized cells in liver, kidney and intestine. The highest expression is found in liver. Expressed in small intestine.

Disease relevance. Dubin-Johnson syndrome (DJS) [MIM:237500] Autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_000383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR005292	MRP	Family
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR050173	ABC_transporter_C-like	Family
IPR056227	TMD0_ABC	Domain

Pfam: PF00005, PF00664, PF24357

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), 6 shown:

• 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)
• taurolithocholate 3-sulfate(in) + ATP + H2O = taurolithocholate 3-sulfate(out) + ADP + phosphate + H(+) (RHEA:50084)
• 17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:60128)
• (4Z,15Z)-bilirubin IXalpha C8-beta-D-glucuronoside(in) + ATP + H2O = (4Z,15Z)-bilirubin IXalpha C8-beta-D-glucuronoside(out) + ADP + phosphate + H(+) (RHEA:66180)
• (4Z,15Z)-bilirubin IXalpha C8,C12-beta-D-bisglucuronoside(in) + ATP + H2O = (4Z,15Z)-bilirubin IXalpha C8,C12-beta-D-bisglucuronoside(out) + ADP + phosphate + H(+) (RHEA:66192)

UniProt features (196 total): helix 67, strand 32, sequence variant 29, topological domain 18, transmembrane region 17, turn 11, modified residue 7, domain 4, glycosylation site 3, mutagenesis site 3, binding site 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
9C12	ELECTRON MICROSCOPY	2.75
8IZQ	ELECTRON MICROSCOPY	3.31
8JXQ	ELECTRON MICROSCOPY	3.32
9BUK	ELECTRON MICROSCOPY	3.4
9BR2	ELECTRON MICROSCOPY	3.41
9JN2	ELECTRON MICROSCOPY	3.44
9JCS	ELECTRON MICROSCOPY	3.47
9JC0	ELECTRON MICROSCOPY	3.52
8JXU	ELECTRON MICROSCOPY	3.55
9JB7	ELECTRON MICROSCOPY	3.55
9JN1	ELECTRON MICROSCOPY	3.56
8JY4	ELECTRON MICROSCOPY	3.58
8JX7	ELECTRON MICROSCOPY	3.6
8IZR	ELECTRON MICROSCOPY	3.62
9C2I	ELECTRON MICROSCOPY	3.62
8JY5	ELECTRON MICROSCOPY	4.17

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92887-F1	81.40	0.38

Functional residue map

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

Ligand- & substrate-binding residues (2): 671–678; 1334–1341

Post-translational modifications (7): 281, 283, 878, 926, 930, 938, 1438

Glycosylation sites (3): 7, 12, 1011

Mutagenesis-validated functional residues (3):

Position	Phenotype
1254	fails to transport methotrexate, leukotriene c4 and estradiol glucuronide.
1254	fails to transport methotrexate and leukotriene c4. does not affect estradiol glucuronide transport.
1254	fails to transport methotrexate; reduces leukotriene c4 transport. does not affect estradiol glucuronide transport.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-189483	Heme degradation
R-HSA-382556	ABC-family protein mediated transport
R-HSA-5679001	Defective ABCC2 causes DJS
R-HSA-9749641	Aspirin ADME
R-HSA-9753281	Paracetamol ADME
R-HSA-9754706	Atorvastatin ADME
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-189445	Metabolism of porphyrins
R-HSA-382551	Transport of small molecules
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-9748784	Drug ADME

MSigDB gene sets: 273 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, REACTOME_METABOLISM_OF_PORPHYRINS, MODULE_418, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOCC_CELL_SURFACE, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT

GO Biological Process (37): glutathione metabolic process (GO:0006749), xenobiotic metabolic process (GO:0006805), xenobiotic transmembrane transport (GO:0006855), gene expression (GO:0010467), negative regulation of gene expression (GO:0010629), mercury ion transport (GO:0015694), bile acid and bile salt transport (GO:0015721), bilirubin transport (GO:0015723), glucuronoside transport (GO:0015779), mRNA metabolic process (GO:0016071), response to insulin (GO:0032868), glutathione transport (GO:0034635), heme catabolic process (GO:0042167), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), xenobiotic export from cell (GO:0046618), cardiac muscle cell differentiation (GO:0055007), transmembrane transport (GO:0055085), response to growth hormone (GO:0060416), transepithelial transport (GO:0070633), leukotriene transport (GO:0071716), proximal tubule development (GO:0072014), response to cisplatin (GO:0072718), transport across blood-brain barrier (GO:0150104), response to peptide (GO:1901652), response to wortmannin (GO:1904567), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961), xenobiotic transport across blood-brain barrier (GO:1990962), lipid transport (GO:0006869), heart development (GO:0007507), response to xenobiotic stimulus (GO:0009410), response to toxic substance (GO:0009636), metal ion transport (GO:0030001), pigment metabolic process (GO:0042440), xenobiotic transport (GO:0042908), response to mercury ion (GO:0046689), carboxylic acid transport (GO:0046942), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (15): ATP binding (GO:0005524), obsolete organic anion transmembrane transporter activity (GO:0008514), ABC-type xenobiotic transporter activity (GO:0008559), bilirubin transmembrane transporter activity (GO:0015127), ABC-type glutathione S-conjugate transporter activity (GO:0015431), ATP hydrolysis activity (GO:0016887), toxin transmembrane transporter activity (GO:0019534), 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), carboxylic acid transmembrane transporter activity (GO:0046943)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), apical plasma membrane (GO:0016324), vesicle (GO:0031982), intercellular canaliculus (GO:0046581), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Drug ADME	3
Metabolism of porphyrins	1
Transport of small molecules	1
ABC transporter disorders	1
Metabolism	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
xenobiotic transport	3
transmembrane transport	3
transmembrane transporter activity	3
response to peptide hormone	2
transport	2
ABC-type transporter activity	2
ATP-dependent activity	2
cellular anatomical structure	2
modified amino acid metabolic process	1
sulfur compound metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
transition metal ion transport	1
detoxification of mercury ion	1
monoatomic cation transmembrane transport	1
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
dicarboxylic acid transport	1
nitrogen compound transport	1
glycoside transport	1
RNA metabolic process	1
tripeptide transport	1
modified amino acid transport	1
sulfur compound transport	1
porphyrin-containing compound catabolic process	1
heme metabolic process	1
pigment catabolic process	1
intracellular signaling cassette	1
export from cell	1
cardiocyte differentiation	1
cardiac muscle tissue development	1
striated muscle cell differentiation	1
cellular process	1
icosanoid transport	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

2606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC2	SLC22A8	Q8TCC7	903
ABCC2	ABCG2	Q9UNQ0	889
ABCC2	SLCO1B1	Q9Y6L6	828
ABCC2	UGT1A6	P19224	822
ABCC2	SLCO1B3	Q9NPD5	801
ABCC2	UGT2B7	P16662	775
ABCC2	CRY1	Q16526	770
ABCC2	SLC10A1	Q14973	769
ABCC2	ATP8B1	O43520	744
ABCC2	SLCO1A2	P46721	739
ABCC2	RDX	P35241	733
ABCC2	SLC35A2	P78381	728
ABCC2	CYP3A4	P05184	727
ABCC2	UGT1A8	Q9HAW9	726
ABCC2	UGT1A1	P22309	725

IntAct

25 interactions, top by confidence:

A	B	Type	Score
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
NFKB1	ABCC2	psi-mi:“MI:0915”(physical association)	0.510
ABCC2	NFKB1	psi-mi:“MI:0915”(physical association)	0.510
ABCC2	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.400
ABCC2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.370
ABCC2	AZIN1	psi-mi:“MI:0915”(physical association)	0.370
ABCC2	MCPH1	psi-mi:“MI:0915”(physical association)	0.370
ABCC2	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
PIGH	ILVBL	psi-mi:“MI:0914”(association)	0.350
TMEM9B	NBAS	psi-mi:“MI:0914”(association)	0.350
KCNE3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
OPALIN	FAM171A2	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	FAAH	psi-mi:“MI:0914”(association)	0.350
S1PR4	NPC1	psi-mi:“MI:0914”(association)	0.350
B4GAT1	KCNN4	psi-mi:“MI:0914”(association)	0.350
CYP26B1	ADCY3	psi-mi:“MI:0914”(association)	0.350
LAIR1	H3-7	psi-mi:“MI:0914”(association)	0.350
CACNG2	CHEK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): ABCC2 (Two-hybrid), ABCC2 (Reconstituted Complex), ABCC2 (Reconstituted Complex), ABCC2 (Co-localization), PDZK1 (Reconstituted Complex), HSPA4 (Reconstituted Complex), TUBB3 (Reconstituted Complex), ABCC2 (Co-localization), ABCC2 (Proximity Label-MS), ABCC2 (Affinity Capture-MS), SLC9A3R1 (Reconstituted Complex), PDZD3 (Reconstituted Complex), ABCC2 (Proximity Label-MS), ABCC2 (Proximity Label-MS), ABCC2 (Proximity Label-MS)

ESM2 similar proteins: A0A125QXJ1, D3ZHR2, E7F6F7, G5EFD4, H2LNR5, O15440, O70595, O75027, P21441, P21958, P33897, P36370, P48410, P70170, P82451, P9WEL8, Q02592, Q08D64, Q09427, Q09428, Q09429, Q10185, Q2UPC0, Q42093, Q4WA92, Q4WPP6, Q61102, Q63120, Q63563, Q704E8, Q751N2, Q7DM58, Q8LPQ6, Q8RY46, Q92887, Q96J65, Q9C8G9, Q9C8H0, Q9C8H1, Q9DC29

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

1 interactions.

A	Effect	B	Mechanism
IRF3	“up-regulates quantity by expression”	ABCC2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1313 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	134
Likely pathogenic	52
Uncertain significance	360
Likely benign	544
Benign	79

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071731	NM_000392.5(ABCC2):c.2556dup (p.Gly853fs)	Pathogenic
1322269	NM_000392.5(ABCC2):c.1882C>T (p.Arg628Ter)	Pathogenic
1333210	NM_000392.5(ABCC2):c.351_355dup (p.Tyr119fs)	Pathogenic
1460184	NC_000010.10:g.(?100177321)(101611388_?)del	Pathogenic
1526158	NM_000392.5(ABCC2):c.584_590del (p.Pro194_Ser195insTer)	Pathogenic
1526242	NM_000392.5(ABCC2):c.3636dup (p.Leu1213fs)	Pathogenic
1917907	NM_000392.5(ABCC2):c.1963C>T (p.Arg655Ter)	Pathogenic
195649	NM_000392.5(ABCC2):c.2901C>A (p.Tyr967Ter)	Pathogenic
2087674	NM_000392.5(ABCC2):c.513del (p.Tyr172fs)	Pathogenic
218946	NM_000392.5(ABCC2):c.1013_1014del (p.Val338fs)	Pathogenic
2692777	NM_000392.5(ABCC2):c.3966T>A (p.Cys1322Ter)	Pathogenic
2697814	NM_000392.5(ABCC2):c.934A>T (p.Lys312Ter)	Pathogenic
2699228	NM_000392.5(ABCC2):c.2458del (p.His820fs)	Pathogenic
2701786	NM_000392.5(ABCC2):c.4285G>T (p.Glu1429Ter)	Pathogenic
2704928	NM_000392.5(ABCC2):c.4333del (p.Leu1445fs)	Pathogenic
2706643	NM_000392.5(ABCC2):c.2992del (p.Leu998fs)	Pathogenic
2715705	NM_000392.5(ABCC2):c.3958del (p.Ile1320fs)	Pathogenic
2719068	NM_000392.5(ABCC2):c.3541C>T (p.Arg1181Ter)	Pathogenic
2724936	NM_000392.5(ABCC2):c.909_921del (p.Lys303fs)	Pathogenic
2735464	NM_000392.5(ABCC2):c.298C>T (p.Arg100Ter)	Pathogenic
2735466	NM_000392.5(ABCC2):c.2026G>C (p.Gly676Arg)	Pathogenic
2735467	NM_000392.5(ABCC2):c.2360_2366del (p.Pro787fs)	Pathogenic
2735469	NM_000392.5(ABCC2):c.3825C>G (p.Tyr1275Ter)	Pathogenic
2735470	NM_000392.5(ABCC2):c.3928C>T (p.Arg1310Ter)	Pathogenic
2735472	NM_000392.5(ABCC2):c.4327C>T (p.Gln1443Ter)	Pathogenic
2735538	NM_000392.5(ABCC2):c.921dup (p.Ser308fs)	Pathogenic
2735805	NM_000392.5(ABCC2):c.2603del (p.Pro868fs)	Pathogenic
2757494	NM_000392.5(ABCC2):c.3533del (p.His1178fs)	Pathogenic
2760020	NM_000392.5(ABCC2):c.1203_1205del (p.Tyr401_Lys402delinsTer)	Pathogenic
2760329	NM_000392.5(ABCC2):c.1074G>A (p.Trp358Ter)	Pathogenic

SpliceAI

4782 predictions. Top by Δscore:

Variant	Effect	Δscore
10:99792352:GCACA:G	donor_gain	1.0000
10:99792358:GG:G	donor_gain	1.0000
10:99792359:GG:G	donor_gain	1.0000
10:99792360:G:GG	donor_gain	1.0000
10:99792360:GTA:G	donor_loss	1.0000
10:99792361:T:G	donor_loss	1.0000
10:99793888:ATAG:A	acceptor_gain	1.0000
10:99794000:G:GG	donor_gain	1.0000
10:99797096:GCATC:G	acceptor_gain	1.0000
10:99797307:TCA:T	donor_gain	1.0000
10:99799347:GTTT:G	donor_gain	1.0000
10:99799368:GAA:G	donor_gain	1.0000
10:99799371:G:GG	donor_gain	1.0000
10:99804106:G:GT	donor_gain	1.0000
10:99805444:CAAG:C	donor_loss	1.0000
10:99805445:AAGG:A	donor_loss	1.0000
10:99805447:GG:G	donor_loss	1.0000
10:99805449:T:G	donor_loss	1.0000
10:99807382:A:AG	acceptor_gain	1.0000
10:99807383:G:GG	acceptor_gain	1.0000
10:99808114:T:TA	acceptor_gain	1.0000
10:99811599:GAGA:G	donor_gain	1.0000
10:99811601:GA:G	donor_gain	1.0000
10:99811603:G:GG	donor_gain	1.0000
10:99817198:T:G	donor_gain	1.0000
10:99817208:T:G	donor_gain	1.0000
10:99819086:TA:T	acceptor_loss	1.0000
10:99819087:A:AC	acceptor_loss	1.0000
10:99819087:A:AG	acceptor_gain	1.0000
10:99819088:G:GA	acceptor_loss	1.0000

AlphaMissense

10172 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:99818802:A:C	S762R	0.999
10:99818804:T:A	S762R	0.999
10:99818804:T:G	S762R	0.999
10:99807439:G:C	R529P	0.998
10:99818821:G:C	R768P	0.998
10:99836119:T:C	L1148P	0.998
10:99843869:G:C	R1271P	0.998
10:99845648:G:C	A1338P	0.998
10:99805410:G:C	R498P	0.997
10:99817338:T:A	W709R	0.997
10:99817338:T:C	W709R	0.997
10:99817429:T:C	L739P	0.997
10:99818830:T:C	L771P	0.997
10:99818833:C:A	A772D	0.997
10:99818893:A:T	D792V	0.997
10:99836125:G:C	R1150P	0.997
10:99847058:T:C	L1415P	0.997
10:99850619:T:C	L1444P	0.997
10:99850673:A:T	E1462V	0.997
10:99850681:G:C	A1465P	0.997
10:99804133:T:A	W442R	0.996
10:99804133:T:C	W442R	0.996
10:99807402:T:A	W517R	0.996
10:99807402:T:C	W517R	0.996
10:99818813:G:C	Q765H	0.996
10:99818813:G:T	Q765H	0.996
10:99831726:T:C	L1000P	0.996
10:99831734:T:A	W1003R	0.996
10:99831734:T:C	W1003R	0.996
10:99844358:T:A	W1294R	0.996

dbSNP variants (sampled 300 via entrez): RS1000031448 (10:99816060 C>G), RS1000068958 (10:99787681 A>G), RS1000137584 (10:99794570 G>A), RS1000140284 (10:99789129 T>C), RS1000263047 (10:99829859 G>A), RS1000294406 (10:99808766 C>A,T), RS1000373193 (10:99851524 A>G), RS1000557033 (10:99845935 C>G,T), RS1000593223 (10:99789553 A>G), RS1000644416 (10:99845386 C>T), RS1000729869 (10:99803236 T>C), RS1000741576 (10:99850068 C>T), RS1000783688 (10:99803845 G>T), RS1000856889 (10:99783465 T>A,C), RS1000864317 (10:99829681 G>C)

Disease associations

OMIM: gene MIM:601107 | disease phenotypes: MIM:237500, MIM:264800

GenCC curated gene-disease

Disease	Classification	Inheritance
Dubin-Johnson syndrome	Strong	Autosomal recessive

Mondo (2): Dubin-Johnson syndrome (MONDO:0009380), autosomal recessive inherited pseudoxanthoma elasticum (MONDO:0009925)

Orphanet (2): Dubin-Johnson syndrome (Orphanet:234), Pseudoxanthoma elasticum (Orphanet:758)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000952	Jaundice
HP:0001080	Biliary tract abnormality
HP:0001392	Abnormality of the liver
HP:0001928	Abnormality of coagulation
HP:0001945	Fever
HP:0002027	Abdominal pain
HP:0002240	Hepatomegaly
HP:0002908	Conjugated hyperbilirubinemia
HP:0004295	Abnormal gastric mucosa morphology
HP:0012086	Abnormal urinary color
HP:0012378	Fatigue

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002411_7	Colorectal cancer	5.000000e-11
GCST003017_4	Colorectal cancer	8.000000e-07
GCST003017_9	Colorectal cancer	4.000000e-08
GCST005351_13	Carboplatin disposition in epthelial ovarian cancer	5.000000e-06
GCST010484_6	Stent thrombosis in response to clopidogrel treatment	1.000000e-06
GCST012020_418	Serum metabolite levels	6.000000e-18
GCST90013407_15	Liver enzyme levels (gamma-glutamyl transferase)	6.000000e-47

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006919	cardiovascular event measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007566	Jaundice, Chronic Idiopathic	C16.320.565.300.764; C16.614.451.500.250; C18.452.648.300.764; C23.550.291.500.479
D011561	Pseudoxanthoma Elasticum	C14.907.454.530; C15.378.463.515.530; C16.131.831.766; C16.320.850.750; C17.300.766; C17.800.804.766; C17.800.827.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885536 (PROTEIN FAMILY), CHEMBL5748 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,495,654 (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
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1096885	VALRUBICIN	4	41,463
CHEMBL1200775	LEUPROLIDE ACETATE	4	68,891
CHEMBL1201182	TEMSIROLIMUS	4	25,195
CHEMBL1272	REPAGLINIDE	4	33,453
CHEMBL1292	CLOFAZIMINE	4	15,481
CHEMBL1541	CEFIXIME	4	27,787
CHEMBL159	VINBLASTINE	4	412,636
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL1660	RIFAPENTINE	4	12,680
CHEMBL178	DAUNORUBICIN	4	203,756
CHEMBL1908360	EVEROLIMUS	4	73,430
CHEMBL269732	TACROLIMUS ANHYDROUS	4	95,168
CHEMBL308954	ETRAVIRINE	4	11,287
CHEMBL374478	RIFAMPIN	4	93,834
CHEMBL387675	DAPTOMYCIN	4	19,735
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL444633	RIFABUTIN	4	27,819
CHEMBL456	ETHACRYNIC ACID	4	20,004
CHEMBL553	ERLOTINIB	4
CHEMBL56337	EPALRESTAT	4
CHEMBL603	ZAFIRLUKAST	4
CHEMBL6067487	IVERMECTIN	4
CHEMBL772	RESERPINE	4
CHEMBL813	EPROSARTAN	4
CHEMBL897	PROBENECID	4
CHEMBL1086218	VALSPODAR	3
CHEMBL1651956	ALISPORIVIR	3
CHEMBL1829174	FASIGLIFAM	3

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

PharmGKB clinical annotations

51 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs113646094	Metabolism/PK	3	pravastatin
rs12762549	Toxicity,Metabolism/PK	3	docetaxel
rs17222723	Toxicity	3	tenofovir	HIV infectious disease
rs17222723	Toxicity	3	doxorubicin	Cardiac rhythm disease;Drug Toxicity;Non-Hodgkin Lymphoma
rs17222723	Toxicity	3	methotrexate	Leukopenia;Osteosarcoma
rs2273697	Other	3	irinotecan	Colorectal Neoplasms
rs2273697	Toxicity	4	tenofovir	HIV infectious disease;Kidney Disorder
rs2273697	Toxicity	4	methotrexate	Rheumatoid arthritis
rs2273697	Toxicity	3	carbamazepine	Epilepsy
rs2273697	Metabolism/PK	3	deferasirox	Beta-thalassemia and related diseases
rs2273697	Efficacy	3	cisplatin;pemetrexed	Mesothelioma
rs2273697	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms
rs2273697	Metabolism/PK	3	ceftriaxone	Central Nervous System Infectious Disorder
rs2273697	Efficacy	3	imatinib	Gastrointestinal Stromal Tumors
rs2273697	Metabolism/PK	3	talinolol
rs2273697	Toxicity	4	antiepileptics;carbamazepine;oxcarbazepine	Epilepsy
rs3740065	Efficacy	3	tamoxifen	Breast Neoplasms
rs3740065	Toxicity	3	Drugs For Treatment Of Tuberculosis	Toxic liver disease;Tuberculosis
rs3740065	Toxicity	3	methotrexate	Acute lymphoblastic leukemia;Burkitt Lymphoma;Drug Toxicity;Lymphoma;Mucositis;Non-Small Cell Lung Carcinoma;Osteosarcoma
rs3740065	Metabolism/PK	4	methotrexate	Acute lymphoblastic leukemia;Burkitt Lymphoma;Osteosarcoma
rs3740066	Toxicity	3	irinotecan	Non-Small Cell Lung Carcinoma
rs3740066	Metabolism/PK	3	carbamazepine	Epilepsy
rs3740066	Metabolism/PK	3	mycophenolic acid	Organ Transplantation
rs3740066	Metabolism/PK	3	tacrolimus	Kidney Transplantation
rs3740066	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms
rs3740066	Efficacy	4	antiepileptics	Epilepsy
rs4148386	Metabolism/PK	3	carbamazepine	Epilepsy
rs717620	Other	3	erythromycin
rs717620	Efficacy	3	atorvastatin	Hypercholesterolemia
rs717620	Metabolism/PK	3	pitavastatin
rs717620	Toxicity	3	tenofovir	HIV infectious disease
rs717620	Efficacy	3	cisplatin;doxorubicin;methotrexate	Osteosarcoma
rs717620	Toxicity	3	methotrexate	Acute lymphoblastic leukemia;Leukemia;Lymphoma;Osteosarcoma
rs717620	Metabolism/PK	3	mycophenolic acid;tacrolimus	Kidney Transplantation
rs717620	Efficacy	4	antiepileptics	Epilepsy
rs717620	Metabolism/PK	4	methotrexate	Acute lymphoblastic leukemia;Lymphoid Leukemia
rs717620	Dosage	3	atorvastatin;simvastatin
rs717620	Toxicity	3	deferasirox	Beta-thalassemia and related diseases
rs717620	Metabolism/PK	3	efavirenz	HIV infectious disease
rs717620	Toxicity	3	atazanavir;lopinavir;ritonavir;tenofovir

PharmGKB variants

36 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs717620	ABCC2	3	3.00	17	pitavastatin;erythromycin;fluorouracil;leucovorin;oxaliplatin;antiepileptics;atorvastatin;atorvastatin;simvastatin;methotrexate;cisplatin;doxorubicin;methotrexate;deferasirox;efavirenz
rs1885301	ABCC2		0.00	0
rs2273697	ABCC2	3	3.00	11	talinolol;antiepileptics;carbamazepine;oxcarbazepine;tenofovir;cisplatin;pemetrexed;imatinib;ceftriaxone;irinotecan;methotrexate;cyclophosphamide;doxorubicin;fluorouracil;deferasirox
rs2804398	ABCC2		0.00	0
rs2804400	ABCC2, NANOGP6		0.00	0
rs2804402	ABCC2		0.00	0
rs3740065	ABCC2	3	3.25	4	methotrexate;tamoxifen;Drugs For Treatment Of Tuberculosis
rs3740066	ABCC2	3	5.50	6	antiepileptics;irinotecan;cyclophosphamide;doxorubicin;fluorouracil;tacrolimus;carbamazepine;mycophenolic acid
rs3740067	ABCC2		0.00	0
rs3758395	ABCC2		0.00	0
rs4148386	ABCC2	3	1.00	1	carbamazepine
rs4148396	ABCC2		0.00	0
rs7080681	ABCC2		0.00	0
rs7910642	ABCC2		0.00	0
rs7917432	ABCC2, RUFY2	3	2.00	1	tenofovir
rs8187707	ABCC2	3	0.25	1	tenofovir
rs8187710	ABCC2	3	2.25	5	tenofovir;lopinavir;calcein;lopinavir;doxorubicin;deferasirox
rs12762549	ABCC2	3	1.00	1	docetaxel
rs17216177	ABCC2		0.00	0
rs17222589	ABCC2		0.00	0
rs17222723	ABCC2	3	2.25	3	doxorubicin;methotrexate;tenofovir
rs113646094	ABCC2	3	1.00	1	pravastatin
rs12826	ABCC2		0.00	0
rs8187692	ABCC2		0.00	0
rs17216198	ABCC2		0.00	0
rs7899457	ABCC2		0.00	0
rs8187706	ABCC2		0.00	0
rs2002042	ABCC2		0.00	0
rs4148398	ABCC2		0.00	0
rs2756109	ABCC2		0.00	0
rs3740074	ABCC2		0.00	0
rs3740063	ABCC2		0.00	0
rs765027508	ABCC2		0.00	0
rs533334893	ABCC2		0.00	0
rs17216317	ABCC2		0.00	0
rs145008610	ABCC2		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
PAK-104P	Inhibition	5.43	pKi

Binding affinities (BindingDB)

3 measured of 4 human assays (4 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
30-ethyl-33-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	IC50	3100 nM	US-9090657: Compound and methods for its production
NSC_60719	KI	8500 nM
25,30-diethyl-33-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,27,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21,24-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	IC50	16000 nM	US-9090657: Compound and methods for its production

ChEMBL bioactivities

22 potent at pChembl≥5 of 84 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.55	IC50	280	nM	BILIRUBIN MONOGLUCURONIDE
6.40	IC50	400	nM	CHEMBL3038248
5.62	IC50	2410	nM	FASIGLIFAM
5.51	IC50	3100	nM	CYCLOSPORINE
5.48	IC50	3300	nM	LEUKOTRIEN C4
5.43	Ki	3700	nM	CHEMBL2074650
5.42	IC50	3850	nM	ETHACRYNIC ACID
5.40	IC50	4000	nM	MK-571
5.39	IC50	4100	nM	CYCLOSPORINE
5.39	IC50	4100	nM	CHEMBL3974624
5.35	IC50	4500	nM	CHEMBL3921707
5.35	IC50	4500	nM	CHEMBL3263914
5.33	Ki	4700	nM	CYCLOSPORINE
5.32	IC50	4800	nM	CHEMBL3263916
5.20	IC50	6300	nM	CHEMBL3263915
5.14	IC50	7300	nM	CHEMBL3964042
5.11	IC50	7800	nM	ETRAVIRINE
5.09	Ki	8110	nM	CYCLOSPORINE
5.09	IC50	8200	nM	CHEMBL3945493
5.05	IC50	9000	nM	CHEMBL3263569
5.00	IC50	1e+04	nM	ERLOTINIB
5.00	IC50	1e+04	nM	MK-571

PubChem BioAssay actives

21 with measured affinity, of 1189 total; 18 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
(5S,6R,7E,9E,11Z,14Z)-6-[(2S)-2-[[(4S)-4-amino-4-carboxybutanoyl]amino]-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-5-hydroxyicosa-7,9,11,14-tetraenoic acid	370719: Inhibition of ABCC2 overexpressed in MDCK cells at 100 uM by flow cytometric-based chloromethylfluorescein-diacetate accumulation assay	ic50	0.1500	uM
(3S,6S)-6-[3-[2-[[3-(2-carboxyethyl)-5-[(Z)-(4-ethenyl-3-methyl-5-oxopyrrol-2-ylidene)methyl]-4-methyl-1H-pyrrol-2-yl]methyl]-5-[(Z)-(3-ethenyl-4-methyl-5-oxopyrrol-2-ylidene)methyl]-4-methyl-1H-pyrrol-3-yl]propanoyloxy]-3,4,5-trihydroxyoxane-2-carboxylic acid	679667: TP_TRANSPORTER: inhibition of LTC4 uptake (LTC4: 0.05 uM) in HepG2 cells	ic50	0.2800	uM
(2S,3R,4S,5S,6S)-6-[3-[2-[[3-[3-[(2S,3S,4R,5R,6R)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy-3-oxopropyl]-5-[(Z)-(3-ethenyl-4-methyl-5-oxopyrrol-2-ylidene)methyl]-4-methyl-1H-pyrrol-2-yl]methyl]-5-[(Z)-(4-ethenyl-3-methyl-5-oxopyrrol-2-ylidene)methyl]-4-methyl-1H-pyrrol-3-yl]propanoyloxy]-3,4,5-trihydroxyoxane-2-carboxylic acid	679667: TP_TRANSPORTER: inhibition of LTC4 uptake (LTC4: 0.05 uM) in HepG2 cells	ic50	0.4000	uM
2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid	1418809: Inhibition of human MRP2	ic50	2.4100	uM
2-(4-benzhydrylpiperazin-1-yl)ethyl 5-[(4R,6R)-4,6-dimethyl-2-oxo-1,3,2lambda5-dioxaphosphinan-2-yl]-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3-carboxylate	678981: TP_TRANSPORTER: inhibition of LTC4 uptake in membrane vesicles from MRP2-expressing LLC PK1 cells	ki	3.7000	uM
Ethacrynic Acid	1473739: Inhibition of human MRP2 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	3.8500	uM
3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoic acid	680797: TP_TRANSPORTER: inhibition of PAH uptake (PAH: 0.1uM) in membrane vesicles from MRP2-expressing HEK cells	ic50	4.0000	uM
(2Z)-2-[[1-(cyclohexylmethyl)-5-methoxyindol-3-yl]methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	4.1000	uM
(2Z)-2-[(5-bromo-1-methylindol-3-yl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	4.5000	uM
(2Z)-2-[(1-butyl-7-methylindol-3-yl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	4.5000	uM
cyclosporine	678981: TP_TRANSPORTER: inhibition of LTC4 uptake in membrane vesicles from MRP2-expressing LLC PK1 cells	ki	4.7000	uM
(2Z)-2-[(1-butyl-5-methylindol-3-yl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	4.8000	uM
(2Z)-2-[(1-butyl-7-methoxyindol-3-yl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	6.3000	uM
(2Z)-2-[[1-[(3-bromophenyl)methyl]-5-methoxyindol-3-yl]methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	7.3000	uM
Etravirine	586880: Inhibition of MRP2 expressed in MDCK2 cells assessed as cell growth inhibition by calcein and pheophorbide A efflux assays	ic50	7.8000	uM
(2Z)-2-[(1-butyl-3-methylindol-2-yl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	8.2000	uM
(2Z)-2-[(1-butylindol-2-yl)methylidene]-4,6-dihydroxy-1-benzofuran-3-one	1327018: Inhibition of ABCC2 (unknown origin) expressed in MDCK2 cells assessed as inhibition of calcein-AM efflux measured after 30 mins in presence of ABCB1 inhibitor GF120918 and ABCC1 inhibitor MK-571 by flow cytometry	ic50	9.0000	uM
Erlotinib	699529: Inhibition of human MRP2	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects response to substance, decreases response to substance, affects cotreatment, increases expression, affects export (+4 more)	20
verlukast	decreases reaction, increases export, affects cotreatment, decreases export, increases transport (+4 more)	13
estradiol-17 beta-glucuronide	increases uptake, affects localization, decreases reaction, affects export, affects transport (+4 more)	11
sodium arsenite	decreases response to substance, affects expression, increases abundance, increases expression, increases reaction	10
Cyclosporine	decreases reaction, increases transport, decreases activity, affects transport, increases abundance (+3 more)	10
Methotrexate	decreases response to substance, increases export, increases expression, affects response to substance, increases response to substance (+4 more)	9
Rifampin	affects export, affects cotreatment, increases expression	9
Acetaminophen	increases expression, affects activity, increases transport, affects cotreatment, decreases expression	7
5(6)-carboxy-2’,7’-dichlorofluorescein	increases reaction, decreases reaction, increases transport, affects binding, increases uptake (+1 more)	6
Probenecid	affects export, decreases reaction, increases export, affects transport, increases reaction (+2 more)	6
sulforaphane	increases expression	5
ochratoxin A	decreases reaction, decreases expression, decreases activity, decreases transport, affects export (+1 more)	5
calcein AM	increases expression, affects transport, increases export, increases transport, decreases reaction	5
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	5
Indomethacin	decreases reaction, decreases export, increases abundance, affects export, affects transport (+2 more)	5
Phenobarbital	affects expression, increases expression	5
Resveratrol	increases reaction, increases expression, decreases expression, affects export, decreases reaction (+1 more)	4
Arsenic Trioxide	decreases expression, increases expression, decreases response to substance	4
Adenosine Triphosphate	decreases reaction, affects metabolic processing, affects activity, increases transport, affects reaction (+2 more)	4
Lithocholic Acid	decreases activity, increases abundance, decreases expression, increases activity, increases expression	4
Mercury	affects transport, increases transport, affects reaction, affects abundance, affects response to substance (+1 more)	4
Aflatoxin B1	decreases methylation, decreases reaction, affects expression, affects cotreatment, decreases expression (+1 more)	4
Paclitaxel	increases export, decreases reaction, affects expression, increases reaction, affects response to substance (+2 more)	4
Leukotriene C4	decreases reaction, increases transport, affects transport	4
beta-Naphthoflavone	increases expression	4
Genistein	decreases reaction, increases expression, affects export, affects binding, increases reaction (+1 more)	4
bisphenol A	affects methylation, affects cotreatment, increases methylation, increases expression, affects expression	3
fluorexon	affects export, affects transport, increases abundance, decreases reaction	3
arsenite	increases abundance, decreases reaction, affects reaction, increases transport, affects transport (+1 more)	3
oltipraz	increases expression	3

ChEMBL screening assays

159 unique, capped per target: 84 functional, 40 admet, 35 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075613	Functional	TP_TRANSPORTER: transepithelial transport (basal to apical) of Phalloidin at a concentration of 1 uM in MRP2- and OATP-C-expressing MDCKII cells	Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. — Naunyn Schmiedebergs Arch Pharmacol
CHEMBL1006005	Binding	Effect on human MRP2-mediated estradiol-17-beta-glucuronide transport in Sf9 cells inverted membrane vesicles relative to control	Prediction and identification of drug interactions with the human ATP-binding cassette transporter multidrug-resistance associated protein 2 (MRP2; ABCC2). — J Med Chem
CHEMBL1743160	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, MRP2	Membrane transporters in drug development. — Nat Rev Drug Discov

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9U72	MDCKII-MRP2/UGT1A1	Spontaneously immortalized cell line	Female
CVCL_A2JY	MDCK2-ABCC2	Spontaneously immortalized cell line	Female
CVCL_B2M0	Abcam A-549 ABCC2 KO	Cancer cell line	Male
CVCL_B5ZV	C2BBe1 MRP2 KO	Cancer cell line	Male
CVCL_B5ZW	C2BBe1 MDR1/MRP2 KO	Cancer cell line	Male
CVCL_B5ZX	C2BBe1 MRP2/BCRP KO	Cancer cell line	Male
CVCL_B6AG	HepaRG MRP2 KO	Cancer cell line	Female
CVCL_B6AH	HepaRG MRP2/MRP4 KO	Cancer cell line	Female
CVCL_X022	MDCK-MRP2	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05832580	PHASE3	RECRUITING	The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum
NCT01525875	PHASE2	COMPLETED	Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)
NCT02537054	PHASE2	COMPLETED	Intravitreal Aflibercept for Therapy of Patients With Pseudoxanthoma Elasticum (PXE)
NCT04441671	PHASE2	WITHDRAWN	Oral Pyrophosphate Absorption in PXE Disease
NCT05569252	PHASE2	COMPLETED	A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
NCT06462547	PHASE2	RECRUITING	ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency
NCT05734196	PHASE1	RECRUITING	The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
NCT00470977	PHASE1/PHASE2	COMPLETED	Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy
NCT05030831	PHASE1/PHASE2	COMPLETED	Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in Adults With ABCC6 Deficiency Causing PXE
NCT00341419	Not specified	COMPLETED	Genetic Analysis of Patients With Pseudoxanthoma Elasticum
NCT00555113	Not specified	COMPLETED	Evolution of Visual Impairment During Pseudoxanthoma Elasticum
NCT01446380	Not specified	UNKNOWN	Phenotypic Expressions in a French Pseudoxanthoma-Elasticum Cohort
NCT01446393	Not specified	COMPLETED	Functional and Structural Characterization of Arteriopathy in Pseudoxanthoma Elasticum (PXE)
NCT01731080	Not specified	UNKNOWN	Arterial Wall Calcium Load in Pseudoxanthoma Elasticum
NCT02108392	Not specified	UNKNOWN	Characterization of Pseudoxanthoma Elasticum
NCT03070860	Not specified	COMPLETED	What’s Happen Under the Calcification Process in Pseudoxanthoma Elasticum
NCT03364504	Not specified	UNKNOWN	Biological Collection of Kidney Cells
NCT03758534	Not specified	UNKNOWN	Natural History of GACI With or Without ARHR2 or PXE
NCT03813550	Not specified	UNKNOWN	Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
NCT04868578	Not specified	RECRUITING	PPI Supplementation to Fight ECtopIc Calcification in PXE
NCT05025722	Not specified	COMPLETED	Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings
NCT05246189	Not specified	COMPLETED	Employment of Patients With Pseudoxanthoma Elasticum
NCT05662085	Not specified	ACTIVE_NOT_RECRUITING	Progression Rate of Pseudoxanthoma Elasticum-associated Choroidal and Retinal Degeneration
NCT06636344	Not specified	RECRUITING	Impact of Optimized Recruitment and Follow-up of Patients With Pseudoxanthoma Elasticum (PXE)
NCT07006649	Not specified	RECRUITING	CHOPXE - Analysis of Choriocapillaris Flow Deficits in Patients With Pseudoxanthoma Elasticum
NCT07048106	Not specified	RECRUITING	Progression Assessment of PXE-associated Alterations
NCT07323082	Not specified	RECRUITING	Purinergic Compounds in Pseudoxanthoma Elasticum