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 hydrolyzes ATP to enable active transport of endogenous and xenobiotic substrates conjugated with glucuronate, glutathione or sulfate.

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): 1,337 total — 132 pathogenic, 58 likely-pathogenic (top 2% of genes corpus-wide)
• GTEx eGene: eQTL in 29 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 12
• ChEMBL bioactivity: 35 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• 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: 14 — 8 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined, 2 protein_coding

MANE Select: ENST00000647814

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 2

ENST00000647814, ENST00000370434, ENST00000496621, ENST00000647836, ENST00000648324, ENST00000648523, ENST00000648689, ENST00000649459, ENST00000649493, ENST00000649932, ENST00001001529, ENST00001001530, ENST00001001531, ENST00001001532

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.

Highest expression (Bgee): lobe of liver, liver, jejunal mucosa, gall bladder, duodenum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ABCC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	sqtl	9.4e-12	-1.22	10:99819413:CTG:C
Testis	eqtl	6.8e-10	-0.29	10:99676961:G:A
Lung	eqtl	2.8e-06	+0.23	10:99761926:G:A
Whole Blood	eqtl	5.9e-06	-0.12	10:99762170:G:C
Brain Cerebellum	eqtl	1.4e-05	-0.53	10:99698196:C:T
Esophagus Mucosa	eqtl	1.8e-05	-0.20	10:99867528:G:T
Cells EBV-transformed lymphocytes	eqtl	3.8e-05	+0.36	10:99755559:T:C
Breast Mammary Tissue	eqtl	8.5e-05	-0.25	10:99613972:C:T
Artery Aorta	eqtl	1.4e-04	+0.20	10:99832563:A:G
Skin Sun Exposed Lower leg	eqtl	2.1e-04	+0.17	10:99829453:A:AT
Esophagus Muscularis	eqtl	2.5e-04	-0.17	10:99998104:G:A
Adipose Subcutaneous	eqtl	2.6e-04	-0.23	10:99613972:C:T
Colon Transverse	eqtl	4.4e-04	-0.18	10:99798989:G:T
Thyroid	eqtl	5.1e-04	-0.19	10:99638682:A:G
Esophagus Gastroesophageal Junction	eqtl	1.1e-03	+0.17	10:99826621:T:G
Colon Sigmoid	eqtl	1.9e-03	-0.19	10:99762170:G:C
Brain Hippocampus	eqtl	2.1e-03	+0.42	10:99634432:A:AATAG
Brain Cerebellar Hemisphere	eqtl	6.7e-03	-0.25	10:99782821:C:T
Spleen	eqtl	7.6e-03	-0.22	10:99798989:G:T
Artery Coronary	eqtl	8.1e-03	-0.41	10:99943051:G:T

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

showing 100 of 286 tissues 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
skin of leg	UBERON:0001511	65.67	gold quality
metanephros	UBERON:0000081	65.18	gold quality
adipose tissue of abdominal region	UBERON:0007808	65.07	gold quality
spleen	UBERON:0002106	64.92	gold quality
body of pancreas	UBERON:0001150	64.77	gold quality
muscle organ	UBERON:0001630	64.49	gold quality
blood	UBERON:0000178	64.12	gold quality
ventricular zone	UBERON:0003053	63.98	gold quality
islet of Langerhans	UBERON:0000006	63.73	gold quality
pancreas	UBERON:0001264	63.55	gold quality
aorta	UBERON:0000947	63.44	gold quality
leukocyte	CL:0000738	63.38	gold quality
monocyte	CL:0000576	63.33	gold quality
mononuclear cell	CL:0000842	63.21	gold quality
bone marrow cell	CL:0002092	63.19	silver quality
skin of abdomen	UBERON:0001416	63.17	gold quality
adipose tissue	UBERON:0001013	62.74	gold quality
left uterine tube	UBERON:0001303	62.70	gold quality
intestine	UBERON:0000160	62.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.31	gold quality
connective tissue	UBERON:0002384	62.17	gold quality
triceps brachii	UBERON:0001509	62.12	gold quality
calcaneal tendon	UBERON:0003701	62.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.91	gold quality
body of stomach	UBERON:0001161	61.85	gold quality
zone of skin	UBERON:0000014	61.72	gold quality
lymph node	UBERON:0000029	61.45	gold quality
left adrenal gland cortex	UBERON:0035825	61.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.21	gold quality
vermiform appendix	UBERON:0001154	61.17	gold quality
lower esophagus	UBERON:0013473	61.14	gold quality
bone marrow	UBERON:0002371	61.13	gold quality
olfactory bulb	UBERON:0002264	60.94	gold quality
type B pancreatic cell	CL:0000169	60.68	gold quality
skeletal muscle tissue	UBERON:0001134	60.55	gold quality
left adrenal gland	UBERON:0001234	60.52	gold quality
ganglionic eminence	UBERON:0004023	60.47	gold quality
left coronary artery	UBERON:0001626	60.44	gold quality
right adrenal gland cortex	UBERON:0035827	60.14	gold quality
right uterine tube	UBERON:0001302	59.90	gold quality
fundus of stomach	UBERON:0001160	59.87	gold quality
coronary artery	UBERON:0001621	59.86	gold quality
stomach	UBERON:0000945	59.72	gold quality
caecum	UBERON:0001153	59.70	gold quality
gluteal muscle	UBERON:0002000	59.68	gold quality
transverse colon	UBERON:0001157	59.60	gold quality
adrenal cortex	UBERON:0001235	59.60	gold quality
urinary bladder	UBERON:0001255	59.48	gold quality
stromal cell of endometrium	CL:0002255	59.36	gold quality
adrenal gland	UBERON:0002369	59.30	gold quality
muscle tissue	UBERON:0002385	59.26	gold quality
right adrenal gland	UBERON:0001233	59.24	gold quality
right coronary artery	UBERON:0001625	59.24	gold quality
upper lobe of left lung	UBERON:0008952	59.21	gold quality
rectum	UBERON:0001052	59.20	gold quality
minor salivary gland	UBERON:0001830	59.17	gold quality
descending thoracic aorta	UBERON:0002345	59.13	gold quality
muscle layer of sigmoid colon	UBERON:0035805	59.09	gold quality
right lung	UBERON:0002167	59.00	gold quality
epithelium of bronchus	UBERON:0002031	58.59	silver quality
bronchial epithelial cell	CL:0002328	58.46	silver quality
thoracic aorta	UBERON:0001515	58.33	gold quality
right lobe of thyroid gland	UBERON:0001119	58.32	gold quality
ascending aorta	UBERON:0001496	58.31	gold quality
esophagus	UBERON:0001043	58.29	gold quality
adrenal tissue	UBERON:0018303	58.07	gold quality
anatomical system	UBERON:0000467	57.93	gold quality
bronchus	UBERON:0002185	57.93	silver quality
material anatomical entity	UBERON:0000465	57.76	gold quality
multicellular organism	UBERON:0000468	57.76	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	113.8	high
Small intestine	tissue	37.9	medium
Duodenum	tissue	36.8	medium
Gallbladder	tissue	23.0	medium
Kidney	tissue	17.3	high
Retina	tissue	3.6
Breast	tissue	2.9	not detected
Cerebellum	tissue	1.7	not detected
Skin 1	tissue	1.6	not detected
Olfactory bulb	tissue	1.5
Amygdala	tissue	1.4
Corpus callosum	tissue	1.4
Cerebral cortex	tissue	1.3	not detected
Retrosplenial cortex	tissue	1.3
Insular cortex	tissue	1.3
Basal ganglia	tissue	1.2	not detected
Retrosplenial and cingulate cortex	tissue	1.2
Temporal cortex	tissue	1.2
Prefrontal cortex	tissue	1.1
Hippocampal formation	tissue	1.1
Entorhinal cortex	tissue	1.1
Ventral forebrain	tissue	1.1
Occipital cortex	tissue	1.1
Motor cortex	tissue	1.0
Putamen	tissue	1.0
Periaqueductal gray	tissue	1.0
Septum	tissue	1.0
Somatosensory cortex	tissue	1.0
Medulla oblongata	tissue	0.9
Substantia nigra	tissue	0.9
Midbrain	tissue	0.8
Hypothalamus	tissue	0.8
Spinal cord	tissue	0.8
Thymus	tissue	0.8
Bone marrow	tissue	0.8	not detected
Lymph node	tissue	0.7	not detected
Pons	tissue	0.7
Tongue	tissue	0.7
Thalamus	tissue	0.7
Superior colliculi	tissue	0.7
Appendix	tissue	0.7	not detected
Skeletal muscle	tissue	0.6	not detected
Nucleus accumbens	tissue	0.6
Testis	tissue	0.5	not detected
Adipose tissue	tissue	0.5	not detected
Vagina	tissue	0.4	not detected
Rectum	tissue	0.4	not detected
Urinary bladder	tissue	0.4	not detected
Pancreas	tissue	0.4	not detected
Placenta	tissue	0.4	not detected
Spleen	tissue	0.4	not detected
Locus coeruleus	tissue	0.4
Hippocampus	tissue	0.4	not detected
Tonsil	tissue	0.4	not detected
Salivary gland	tissue	0.3	medium
Colon	tissue	0.3	not detected
Fallopian tube	tissue	0.3	not detected
Stomach 1	tissue	0.2
Seminal vesicle	tissue	0.2	not detected
Smooth muscle	tissue	0.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (1.4), Parieto-temporal junction (white matter) (1.1), Subiculum (1.1), Ventral hippocampus (1.1), Dorsal hippocampus (1.0).

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)

Targeting ABCC2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 57 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.55e-45, LOEUF 0.985, missense Z 1.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000647814 — one region, missense o/e 0.98.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1352447) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating bilirubin level	5
abnormal liver physiology	2
abnormal bile secretion	2
increased circulating cholesterol level	2
bilirubinuria	2
increased neutrophil cell number	1
increased circulating HDL cholesterol level	1
abnormal kidney physiology	1
decreased mean corpuscular volume	1
decreased hemoglobin content	1
increased circulating alanine transaminase level	1
decreased circulating alkaline phosphatase level	1
increased liver weight	1
increased kidney weight	1
abnormal bile composition	1
decreased lymphocyte cell number	1
increased circulating aspartate transaminase level	1
decreased mean corpuscular hemoglobin	1
increased physiological sensitivity to xenobiotic	1
abnormal xenobiotic pharmacokinetics	1
decreased mean platelet volume	1
abnormal blood homeostasis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2XCD4	100.0%	Diamond
Saccharomyces cerevisiae S288C	P0CE69	100.0%	Diamond
Oryza sativa Japonica Group	Q10RX7	100.0%	Diamond
Oryctolagus cuniculus	P82451	98.1%	Diamond
Cricetus cricetus	Q09427	98.0%	Diamond
Macaca fascicularis	Q864R9	97.6%	Diamond
Arabidopsis thaliana	Q7FB56	94.8%	Diamond
Canis lupus familiaris	Q6UR05	93.1%	Diamond
Bos taurus	Q8HXQ5	93.1%	Diamond
Zea mays	A7KVC2	90.5%	Diamond
Dictyostelium discoideum	Q8ST87	86.2%	Diamond
Gallus gallus	Q5F364	79.0%	Diamond
Schizosaccharomyces pombe 972h-	Q10185	63.4%	Diamond
Nakaseomyces glabratus CBS 138	Q6FWS5	55.3%	Diamond
Pyricularia oryzae 70-15	G4N2B5	47.9%	Diamond
Cryptococcus neoformans H99	J9VQH1	42.5%	Diamond
Mycosarcoma maydis	A0A0D1CZ63	41.8%	Diamond
Talaromyces islandicus	A0A0U1LQE1	41.3%	Diamond
Aspergillus versicolor	P9WEL8	41.0%	Diamond
Candida albicans SC5314	Q5A762	41.0%	Diamond
Aspergillus nidulans FGSC A4	A0A1U8QTJ9	40.6%	Diamond
Leishmania tarentolae	P21441	40.3%	Diamond
Escherichia coli	Q9X2W0	36.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DNMBP	protein-coding	23268
CUTC	protein-coding	51076
SLC25A28-DT	ncRNA	123466211
COX15	protein-coding	1355
ENTPD7	protein-coding	57089
SLC25A28	protein-coding	81894
DNMBP-AS1	ncRNA	100188954
CPN1	protein-coding	1369

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 hydrolyzes ATP to enable active transport of endogenous and xenobiotic substrates conjugated with glucuronate, glutathione or sulfate. Operates at apical membranes of polarized cells such as hepatocytes, renal and intestinal epithelial cells, where it mediates hepatobiliary and renal excretion of conjugated substrates preventing them from being recycled back into the bloodstream. Involved in canalicular bile production. Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin, enabling bilirubin detoxification. Mediates the efflux of steroid glucuronates and may regulate their hepatobiliary and renal metabolic clearance. Displays low affinity but high transport velocity toward androgen conjugates such as testosterone and dihydrotestosterone glucuronates as well as toward estrogen conjugates including estradiol, estrone and estriol glucuronates. May control the hepatobiliary and renal efflux of inflammatory leukotriene C4 (LTC4) and related cysteinyl leukotrienes. Transports sulfated bile salt such as taurolithocholate sulfate. It is functionally inactive toward androgen sulfates. Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors. Can confer resistance to several anticancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine, by decreasing accumulation of these drugs in cells.

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)

• 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)
• (4Z,15Z)-bilirubin IXalpha C12-beta-D-glucuronoside(in) + ATP + H2O = (4Z,15Z)-bilirubin IXalpha C12-beta-D-glucuronoside(out) + ADP + phosphate + H(+) (RHEA:79155)
• 3beta-androst-5-en-17-one 3-O-(beta-D-glucuronate)(in) + ATP + H2O = 3beta-androst-5-en-17-one 3-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:86835)
• epitestosterone 17-O-(beta-D-glucuronate)(in) + ATP + H2O = epitestosterone 17-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:86839)
• 3alpha-hydroxyetiocholan-17-one 3-O-(beta-D-glucuronate)(in) + ATP + H2O = 3alpha-hydroxyetiocholan-17-one 3-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:86843)
• testosterone 17-O-(beta-D-glucuronate)(in) + ATP + H2O = testosterone 17-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:86847)
• estrone 3-O-(beta-D-glucuronate)(in) + ATP + H2O = estrone 3-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:86851)

UniProt features (206 total): helix 77, 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 by resolution:

PDB	Title	Method	Resolution (Å)
9C12	Leukotriene C4-bound Multidrug Resistance-associated Protein 2 (MRP2)	ELECTRON MICROSCOPY	2.75
8IZQ	Multidrug resistance-associated protein 3	ELECTRON MICROSCOPY	3.31
8JXQ	Cryo-EM structure of bilirubin ditaurate (BDT) bound human ABC transporter ABCC2	ELECTRON MICROSCOPY	3.32
9BUK	Outward-facing, ATP-bound Multidrug Resistance-associated Protein 2 (MRP2) (E1462Q)	ELECTRON MICROSCOPY	3.4
9BR2	Inward-facing, ATP-bound Multidrug Resistance-associated Protein 2 (MRP2) (E1462Q)	ELECTRON MICROSCOPY	3.41
9JN2	Multidrug resistance-associated protein 2 in complex with AMP-PNP in active state	ELECTRON MICROSCOPY	3.44
9JCS	Multidrug resistance-associated protein 2 in complex with MK-571	ELECTRON MICROSCOPY	3.47
9JC0	Multidrug resistance-associated protein 2 in complex with MK-571 and ATP	ELECTRON MICROSCOPY	3.52
8JXU	Cryo-EM structure of human ABC transporter ABCC2 under active turnover condition	ELECTRON MICROSCOPY	3.55
9JB7	Multidrug resistance-associated protein 2 in complex with SN-38G	ELECTRON MICROSCOPY	3.55
9JN1	apo Multidrug resistance-associated protein 2 in complex with AMP-PNP in rest state	ELECTRON MICROSCOPY	3.56
8JY4	Cryo-EM structure of human ABC transporter ABCC2 in apo’ state	ELECTRON MICROSCOPY	3.58
8JX7	Cryo-EM structure of human ABC transporter ABCC2	ELECTRON MICROSCOPY	3.6
8IZR	Multidrug resistance-associated protein 2	ELECTRON MICROSCOPY	3.62
9C2I	Inward-facing, ligand-free Multidrug Resistance-associated protein 2 (MRP2)	ELECTRON MICROSCOPY	3.62
8JY5	Cryo-EM structure of human ABC transporter ABCC2 in apo” state	ELECTRON MICROSCOPY	4.17

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Metabolic proteins, Transporters, Primary Active Transporters, Predicted membrane proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of cofactor/vitamin metabolism

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
671–678	ATP
1334–1341	ATP

Post-translational modifications (7)

Type	Positions
Phosphoserine	281, 283, 878, 926, 930, 938, 1438

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	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

6 curated (TAS) of 13; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

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

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 (14): xenobiotic metabolic process (GO:0006805), xenobiotic transmembrane transport (GO:0006855), negative regulation of gene expression (GO:0010629), bile acid and bile salt transport (GO:0015721), bilirubin transport (GO:0015723), heme catabolic process (GO:0042167), xenobiotic export from cell (GO:0046618), transmembrane transport (GO:0055085), transepithelial transport (GO:0070633), leukotriene transport (GO:0071716), transport across blood-brain barrier (GO:0150104), xenobiotic transport across blood-brain barrier (GO:1990962), lipid transport (GO:0006869), carboxylic acid transport (GO:0046942)

GO Molecular Function (12): ATP binding (GO:0005524), 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), transmembrane transporter activity (GO:0022857), ATPase-coupled transmembrane transporter activity (GO:0042626), xenobiotic transmembrane transporter activity (GO:0042910), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), protein binding (GO:0005515)

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

7 top-level categories:

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

48 GO namespaces:

Category	Terms
xenobiotic transport	4
transmembrane transport	3
transport	3
ABC-type transporter activity	2
ATP-dependent activity	2
transmembrane transporter activity	2
cellular anatomical structure	2
metabolic process	1
cellular response to xenobiotic stimulus	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
dicarboxylic acid transport	1
nitrogen compound transport	1
porphyrin-containing compound catabolic process	1
heme metabolic process	1
pigment catabolic process	1
export from cell	1
cellular process	1
icosanoid transport	1
vascular transport	1
transport across blood-brain barrier	1
lipid localization	1
organic acid transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
xenobiotic transmembrane transporter activity	1
dicarboxylic acid transmembrane transporter activity	1
bilirubin transport	1
sulfur compound transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
transporter activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
membrane-bounded organelle	1
cell-cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
bile acid and bile salt transport	BP	mutant phenotype
bilirubin transport	BP	mutant phenotype
heme catabolic process	BP	mutant phenotype
leukotriene transport	BP	mutant phenotype
xenobiotic export from cell	BP	mutant phenotype
xenobiotic transmembrane transport	BP	mutant phenotype
apical plasma membrane	CC	direct assay
cell surface	CC	direct assay
ABC-type glutathione S-conjugate transporter activity	MF	mutant phenotype
ABC-type xenobiotic transporter activity	MF	mutant phenotype
ATPase-coupled transmembrane transporter activity	MF	direct assay
bilirubin transmembrane transporter activity	MF	mutant phenotype
xenobiotic transmembrane transporter activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,636 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC2	SLC22A8	Q8TCC7	896
ABCC2	ABCG2	Q9UNQ0	888
ABCC2	SLCO1B1	Q9Y6L6	798
ABCC2	SLCO1B3	Q9NPD5	768
ABCC2	SLC10A1	Q14973	752
ABCC2	SLCO1A2	P46721	719
ABCC2	CYP3A4	P05184	719
ABCC2	UGT1A6	P19224	716
ABCC2	UGT1A1	P22309	716
ABCC2	SLCO2B1	O94956	715
ABCC2	UGT1A7	Q9HAW7	715
ABCC2	UGT1A8	Q9HAW9	715
ABCC2	NR1I2	O75469	705
ABCC2	UGT1A4	P22310	702
ABCC2	UGT1A10	Q9HAW8	701

IntAct

Human interaction partners of ABCC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
NFKB1	physical association	0.510	3
HNRNPDL	physical association	0.400	1
AZIN1	physical association	0.370	1
MCPH1	physical association	0.370	1
SHANK3	physical association	0.370	1
UBQLN1	physical association	0.370	1

BioGRID (96 interactions; top human partners by supporting records): PDZK1 (Two-hybrid; 3 records), SLC9A3R1 (Reconstituted Complex; 3 records), NFKB1 (Affinity Capture-Western; 2 records), ABCA3 (Co-fractionation), ABCC4 (Co-fractionation), AP2M1 (Affinity Capture-Western), ATP11C (Co-fractionation), ATP6V1B1 (Co-fractionation), ATP6V1E1 (Co-fractionation), AZIN1 (Two-hybrid), B4GAT1 (Affinity Capture-MS), CACNG2 (Affinity Capture-MS), CHCHD2 (Co-fractionation), CLTC (Affinity Capture-Western), CYP26B1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for ABCC2: 1,337 ClinVar records (190 pathogenic / likely pathogenic); 51 PharmGKB clinical annotations; 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,337 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	132
Likely pathogenic	58
Uncertain significance	370
Likely benign	549
Benign	75

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 190 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
8418	NM_000392.5(ABCC2):c.3517A>T (p.Ile1173Phe)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
290862	NM_000392.5(ABCC2):c.3399_3400del (p.Tyr1134fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
595904	NM_000392.5(ABCC2):c.3216dup (p.Asp1073Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
818031	NM_000392.5(ABCC2):c.4239_4240dup (p.His1414fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
195649	NM_000392.5(ABCC2):c.2901C>A (p.Tyr967Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
593171	NM_000392.5(ABCC2):c.2260del (p.Ile754fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
593738	NM_000392.5(ABCC2):c.3538C>T (p.Gln1180Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
593794	NM_000392.5(ABCC2):c.2325del (p.Tyr776fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
598367	NM_000392.5(ABCC2):c.2443C>T (p.Arg815Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2735469	NM_000392.5(ABCC2):c.3825C>G (p.Tyr1275Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2735470	NM_000392.5(ABCC2):c.3928C>T (p.Arg1310Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
498026	NM_000392.5(ABCC2):c.3220_3226del (p.Thr1074fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
498804	NM_000392.5(ABCC2):c.3599G>A (p.Trp1200Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
498805	NM_000392.5(ABCC2):c.3500dup (p.Ser1168fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
501700	NM_000392.5(ABCC2):c.476del (p.Asn159fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore ABCC2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 2,644):

Position(s)	Effect	Δscore	Sites
10:99792360–99792361	donor_loss	1.0000	5
10:99805448–99805449	donor_loss	1.0000	5
10:99817198	donor_gain	1.0000
10:99817208	donor_gain	1.0000
10:99830305–99830306	acceptor_loss	1.0000	6
10:99830434	donor_loss	1.0000	3
10:99843797–99843798	acceptor_loss	1.0000	3
10:99843901–99843902	donor_loss	1.0000	5
10:99844316	acceptor_gain	1.0000
10:99844320–99844321	acceptor_loss	1.0000	5

AlphaMissense

3,076 missense substitutions predicted likely pathogenic (of 10,172 scored), across 909 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D792	8	0.991	0.997
D785	8	0.980	0.993
D1461	8	0.980	0.993
H1493	8	0.980	0.994
D427	8	0.977	0.989
D742	8	0.974	0.987
S762	8	0.970	0.999
D1092	8	0.970	0.991
D1468	8	0.965	0.989
D786	8	0.956	0.989
D1087	8	0.952	0.988
F580	8	0.951	0.993
D496	8	0.950	0.990
F1348	8	0.934	0.984
F562	8	0.928	0.980
F1387	8	0.922	0.984
F586	8	0.920	0.981
F721	8	0.914	0.977
D1361	8	0.910	0.981
S1438	8	0.910	0.994

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	5.77e-07
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	5.54e-05

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Dubin-Johnson syndrome	Strong	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Cholestasis	green
Neonatal cholestasis	green

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 phenotypes (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:

Study	Trait	p-value
GCST90013407_155	Liver enzyme levels (gamma-glutamyl transferase)	6e-47
GCST012020_372	Serum metabolite levels	6e-18
GCST002411_7	Colorectal cancer	5e-11
GCST003017_9	Colorectal cancer	4e-8
GCST003017_4	Colorectal cancer	8e-7
GCST010484_6	Stent thrombosis in response to clopidogrel treatment	1e-6
GCST005351_13	Carboplatin disposition in epthelial ovarian cancer	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

MeSH disease descriptors

2 disease descriptors:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,358,927 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

35 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL388590	BENZBROMARONE	4	8,286
CHEMBL1541	CEFIXIME	4	28,030
CHEMBL1292	CLOFAZIMINE	4	15,677
CHEMBL160	CYCLOSPORINE	4	169,776
CHEMBL387675	DAPTOMYCIN	4	19,963
CHEMBL178	DAUNORUBICIN	4	205,873
CHEMBL56337	EPALRESTAT	4	111
CHEMBL813	EPROSARTAN	4	19,625
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL456	ETHACRYNIC ACID	4	20,123
CHEMBL308954	ETRAVIRINE	4	11,476
CHEMBL1908360	EVEROLIMUS	4	74,649
CHEMBL6067487	IVERMECTIN	4
CHEMBL1200775	LEUPROLIDE ACETATE	4	69,527
CHEMBL897	PROBENECID	4	105,849
CHEMBL1272	REPAGLINIDE	4	33,658
CHEMBL772	RESERPINE	4	330,863
CHEMBL444633	RIFABUTIN	4	28,036
CHEMBL374478	RIFAMPIN	4	94,660
CHEMBL1660	RIFAPENTINE	4	12,885
CHEMBL1617	RIFAXIMIN	4
CHEMBL1064	SIMVASTATIN	4
CHEMBL269732	TACROLIMUS ANHYDROUS	4
CHEMBL1201182	TEMSIROLIMUS	4
CHEMBL1096885	VALRUBICIN	4
CHEMBL159	VINBLASTINE	4
CHEMBL603	ZAFIRLUKAST	4
CHEMBL1651956	ALISPORIVIR	3
CHEMBL1829174	FASIGLIFAM	3
CHEMBL77305	RUBITECAN	3
CHEMBL265502	SURAMIN	3
CHEMBL1086218	VALSPODAR	3
CHEMBL4297270	BMS-986020	2
CHEMBL2013174	VEDROPREVIR	2
CHEMBL3314565	AZD-5099	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

51 annotations by evidence level (1 strongest → 4):

Variant	Association	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	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
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
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
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	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
rs717620	Efficacy	3	tamoxifen	Breast Neoplasms
rs717620	Toxicity	3	fluorouracil;leucovorin;oxaliplatin	Colonic Neoplasms
rs717620	Toxicity	3	fluorouracil;leucovorin;oxaliplatin	Colorectal Neoplasms
rs717620	Toxicity	3	sorafenib	Exanthema
rs7917432	Toxicity	3	tenofovir	HIV infectious disease
rs8187707	Toxicity	3	tenofovir	HIV infectious disease
rs8187710	Toxicity	3	doxorubicin	Non-Hodgkin Lymphoma
rs8187710	Other	3	calcein;lopinavir
rs8187710	Efficacy	3	lopinavir	HIV infectious disease
rs8187710	Toxicity	3	deferasirox	Beta-thalassemia and related diseases
rs2273697	Toxicity	4	tenofovir	HIV infectious disease;Kidney Disorder
rs2273697	Toxicity	4	methotrexate	Rheumatoid arthritis
rs2273697	Toxicity	4	antiepileptics;carbamazepine;oxcarbazepine	Epilepsy
rs3740065	Metabolism/PK	4	methotrexate	Acute lymphoblastic leukemia;Burkitt Lymphoma;Osteosarcoma
rs3740066	Efficacy	4	antiepileptics	Epilepsy
rs717620	Efficacy	4	antiepileptics	Epilepsy
rs717620	Metabolism/PK	4	methotrexate	Acute lymphoblastic leukemia;Lymphoid Leukemia
rs8187710	Toxicity	4	tenofovir	Fanconi renotubular syndrome;HIV infectious disease

PharmGKB variants

11 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
rs2273697	ABCC2	3	3.00	11	talinolol;antiepileptics;carbamazepine;oxcarbazepine;tenofovir;cisplatin;pemetrexed;imatinib;ceftriaxone;irinotecan;methotrexate;cyclophosphamide;doxorubicin;fluorouracil;deferasirox
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
rs4148386	ABCC2	3	1.00	1	carbamazepine
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
rs17222723	ABCC2	3	2.25	3	doxorubicin;methotrexate;tenofovir
rs113646094	ABCC2	3	1.00	1	pravastatin

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

showing 59 of 119 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs717620	methotrexate	Toxicity	Allele T is associated with increased risk of Drug Toxicity when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.	PMID:24404132
rs717620	methotrexate	Metabolism/PK	Allele T is associated with decreased clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.	PMID:24404132
rs3740065	methotrexate	Metabolism/PK	Genotypes AG + GG are associated with increased plasma level when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA.	PMID:23222202
rs2273697	carbamazepine, oxcarbazepine	Efficacy	Genotype AG is associated with resistance to carbamazepine or oxcarbazepine in people with Epilepsy as compared to genotype GG.	PMID:25155934
rs2273697	deferasirox	Metabolism/PK	Genotype AG is associated with increased concentrations of deferasirox in people with beta-Thalassemia as compared to genotype GG.	PMID:25348619
rs8187710	cyclophosphamide, epirubicin, paclitaxel	Toxicity	Allele A is associated with decreased likelihood of Peripheral Nervous System Diseases when treated with cyclophosphamide, epirubicin and paclitaxel in women with Breast Neoplasms as compared to allele G.	PMID:24599932
rs17222723	cyclophosphamide, epirubicin, paclitaxel	Toxicity	Allele A is associated with decreased likelihood of Peripheral Nervous System Diseases when treated with cyclophosphamide, epirubicin and paclitaxel in women with Breast Neoplasms as compared to allele T.	PMID:24599932
rs3740065	cyclosporine, methotrexate	Efficacy	Genotype AA is associated with increased risk of Graft vs Host Disease when treated with cyclosporine and methotrexate in people with Hematopoietic stem cell transplantation as compared to genotype AG.	PMID:25425682
rs717620	tamoxifen	Efficacy	Genotype CT is associated with increased response to tamoxifen in women Breast Neoplasms as compared to genotype CC.	PMID:27110128
rs3740066	mycophenolic acid	Metabolism/PK	Genotype CT is associated with decreased concentrations of mycophenolic acid in people with lung transplantation as compared to genotypes CC + TT.	PMID:26307985
rs3740066	vincristine	Toxicity	Allele T is associated with decreased likelihood of Neurotoxicity Syndromes when treated with vincristine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.	PMID:27180762
rs12826	vincristine	Toxicity	Allele T is associated with decreased likelihood of Neurotoxicity Syndromes when treated with vincristine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.	PMID:27180762
rs717620	sorafenib	Toxicity	Genotype CC is associated with increased risk of Exanthema when treated with sorafenib in people with Carcinoma, Renal Cell as compared to genotype CT.	PMID:23237922
rs717620	antiepileptics	Efficacy	Genotypes CT + TT are associated with increased resistance to antiepileptics in people with Epilepsy as compared to genotype CC.	PMID:27816260
rs2273697	deferasirox	Metabolism/PK	Genotype AG is associated with increased exposure to deferasirox in children with beta-Thalassemia as compared to genotype GG.	PMID:28346059
rs717620	diclofenac	Toxicity	Allele T is associated with increased likelihood of Toxic liver disease when treated with diclofenac as compared to allele C.	PMID:17241877
rs8187710	lumefantrine	Metabolism/PK	Genotype AA is associated with increased concentrations of lumefantrine in children with Malaria as compared to genotypes AG + GG.	PMID:28639487
rs2273697	mycophenolic acid	Metabolism/PK	Allele A is associated with decreased exposure to mycophenolic acid in people with Kidney Transplantation as compared to allele G.	PMID:28624888
rs2273697	mycophenolic acid	Metabolism/PK	Allele A is associated with decreased exposure to mycophenolic acid as compared to allele G.	PMID:28624888
rs717620	mycophenolic acid	Metabolism/PK	Allele T is associated with exposure to mycophenolic acid in people with Kidney Transplantation as compared to allele C.	PMID:28624888
rs717620	atorvastatin	Efficacy	Genotypes CT + TT are associated with decreased response to atorvastatin in men with Hypercholesterolemia as compared to genotype CC.	PMID:29178257
rs3740066	tacrolimus	Metabolism/PK	Genotypes CT + TT is associated with increased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotype CC.	PMID:28316087
rs717620	tacrolimus	Metabolism/PK	Genotypes CT + TT is associated with increased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotype CC.	PMID:28316087
rs3740066	tacrolimus	Metabolism/PK	Genotypes CT + TT is associated with decreased dose of tacrolimus in people with Kidney Transplantation as compared to genotype CC.	PMID:28316087
rs3740066	methotrexate	Metabolism/PK	Genotype TT is associated with decreased concentrations of methotrexate in children with Osteosarcoma as compared to genotypes CC + CT.	PMID:27566582
rs2273697	methotrexate	Toxicity	Allele A is associated with increased risk of Bone Marrow Diseases when treated with methotrexate in children with Osteosarcoma as compared to allele G.	PMID:27566582
rs717620	voriconazole	Metabolism/PK	Genotypes CT + TT is associated with increased trough concentration of voriconazole in children as compared to genotype CC.	PMID:29914286
rs2273697	cyclophosphamide, doxorubicin, fluorouracil	Toxicity	Genotype GG is associated with increased risk of Anemia when treated with cyclophosphamide, doxorubicin and fluorouracil in women with Breast Neoplasms as compared to genotypes AA + AG.	PMID:29507678
rs3740066	cyclophosphamide, doxorubicin, fluorouracil	Toxicity	Genotype TT is associated with increased risk of Neutropenia when treated with cyclophosphamide, doxorubicin and fluorouracil in women with Breast Neoplasms as compared to genotypes CC + CT.	PMID:29507678
rs3740066	cyclophosphamide, doxorubicin, fluorouracil	Toxicity	Genotypes CT + TT are associated with increased risk of Nausea when treated with cyclophosphamide, doxorubicin and fluorouracil in women with Breast Neoplasms as compared to genotype CC.	PMID:29507678
rs8187692	rosuvastatin	Metabolism/PK	Allele A is associated with increased exposure to rosuvastatin in healthy individuals as compared to allele G.	PMID:30100615
rs17216198	rosuvastatin	Metabolism/PK	Allele T is associated with decreased exposure to rosuvastatin in healthy individuals as compared to allele C.	PMID:30100615
rs3740066	rosuvastatin	Metabolism/PK	Allele T is associated with decreased exposure to rosuvastatin in healthy individuals as compared to allele C.	PMID:30100615
rs7899457	rosuvastatin	Metabolism/PK	Allele T is associated with decreased exposure to rosuvastatin in healthy individuals as compared to allele C.	PMID:30100615
rs8187706	rosuvastatin	Metabolism/PK	Allele A is associated with decreased exposure to rosuvastatin in healthy individuals as compared to allele G.	PMID:30100615
rs17216177	rosuvastatin	Metabolism/PK	Allele C is associated with decreased exposure to rosuvastatin in healthy individuals as compared to allele T.	PMID:30100615
rs8187710	rosuvastatin	Metabolism/PK	Allele A is associated with decreased exposure to rosuvastatin in healthy individuals as compared to allele G.	PMID:30100615
rs717620	mycophenolic acid	Metabolism/PK	Genotype TT is associated with increased dose-adjusted trough concentrations of mycophenolic acid in people with Kidney Transplantation as compared to genotypes CC + CT.	PMID:30345879
rs717620	simvastatin	Efficacy	Genotypes CT + TT is associated with decreased response to simvastatin in people with Hypercholesterolemia as compared to genotype CC.	PMID:30024814
rs2273697	imatinib	Efficacy	Genotype GG is associated with decreased progression-free survival when treated with imatinib in people with Gastrointestinal Stromal Tumors as compared to genotypes AA + AG.	PMID:30237583
rs2273897	emtricitabine	Metabolism/PK	Genotype TT is associated with increased concentrations of emtricitabine in people with HIV Infections and Pregnancy as compared to genotypes CC + CT.	PMID:30767719
rs717620	pitavastatin	Metabolism/PK	Allele T is associated with decreased exposure to pitavastatin in healthy individuals as compared to allele C.	PMID:23007012
rs717620	tenofovir disoproxil fumarate	Toxicity	Genotype TT is associated with increased severity of nephrotoxicity due to tenofovir disoproxil fumarate in people with HIV Infections as compared to genotypes CC + CT.	PMID:31619748
rs3740065	Drugs For Treatment Of Tuberculosis	Toxicity	Genotypes AG + GG are associated with decreased risk of Toxic liver disease due to Drugs For Treatment Of Tuberculosis in people with Tuberculosis as compared to genotype AA.	PMID:31648372
rs2273697	atorvastatin	Efficacy	Genotype AG is associated with decreased response to atorvastatin in healthy individuals as compared to genotype GG.	PMID:28435225
rs717620	methotrexate	Metabolism/PK	Genotypes CT + TT are associated with decreased concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.	PMID:31870219
rs717620	methotrexate	Toxicity	Genotypes CT + TT are associated with increased risk of Leukopenia when treated with methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.	PMID:31870219
rs717620	cisplatin, doxorubicin, methotrexate	Efficacy	Genotypes CT + TT is associated with decreased response to cisplatin, doxorubicin and methotrexate in people with Osteosarcoma as compared to genotype CC.	PMID:21887680
rs17222723	methotrexate	Toxicity	Genotypes AT + TT are associated with increased risk of Leukopenia when treated with methotrexate in people with Osteosarcoma as compared to genotype AA.	PMID:21887680
rs717620	methotrexate	Toxicity	Genotypes CT + TT is associated with decreased discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to genotype CC.	PMID:34575187
rs3740066	anthracyclines and related substances	Toxicity	Genotype TT is associated with increased likelihood of febrile neutropenia when treated with anthracyclines and related substances in people with Soft Tissue Neoplasms and Sarcoma as compared to genotypes CC + CT.	PMID:35455734
rs3740066	anthracyclines and related substances	Efficacy	Genotype TT is associated with decreased overall survival when treated with anthracyclines and related substances in people with Soft Tissue Neoplasms and Sarcoma as compared to genotypes CC + CT.	PMID:35455734
rs2273697	anthracyclines and related substances	Efficacy	Genotypes AG + GG is associated with increased Recurrence free survival when treated with anthracyclines and related substances in people with Soft Tissue Neoplasms and Sarcoma as compared to genotype AA.	PMID:35455734
rs3740066	tacrolimus	Metabolism/PK	Genotype TT is associated with increased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotype CC.	PMID:36118414
rs2273697	lacosamide	Efficacy	Allele A is associated with increased resistance to lacosamide in children with Epilepsy as compared to allele G.	PMID:36253887
rs717620	lacosamide	Efficacy	Allele T is associated with increased resistance to lacosamide in children with Epilepsy as compared to allele C.	PMID:36253887
rs2273697	lacosamide	Metabolism/PK	Genotype GG is associated with increased concentrations of lacosamide in children with Epilepsy as compared to genotypes AA + AG.	PMID:36253887
rs717620	lacosamide	Metabolism/PK	Genotype CC is associated with increased concentrations of lacosamide in children with Epilepsy as compared to genotypes CT + TT.	PMID:36253887
rs2273697	rasagiline	Metabolism/PK	Genotype AA is associated with decreased clearance of rasagiline in healthy individuals as compared to genotypes AG + GG.	PMID:36297437

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)

164 measured of 601 human assays (649 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(2-{4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]piperidin-1-yl}ethyl)imidazolidin-2-one	KI	0.38 nM
(2S)-1-[[4-(difluoromethyl)-6-[2-(difluoromethyl)-4-pyridinyl]-3-pyridinyl]oxy]-2,4-dimethylpentan-2-amine	IC50	0.5 nM	US-10155760: Biaryl kinase inhibitors
2,2-dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one	IC50	0.9 nM
escitalopram	KI	1 nM
cid_1548953	KI	1 nM
(2S)-1-[[2-(difluoromethyl)-6-[2-(difluoromethyl)-4-pyridinyl]-3-pyridinyl]oxy]-2,4-dimethylpentan-2-amine	IC50	1.2 nM	US-10155760: Biaryl kinase inhibitors
(1R)-N-(prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine	KI	1.4 nM
4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol	EC50	1.5 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.6 nM
CHEMBL195	KI	1.6 nM
(S)-4-((3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)methyl)oxazolidin-2-one	KD	1.8 nM
Permax	KI	1.91 nM
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile	IC50	2 nM	US-9284315: Three-ring PI3K and/or mTOR inhibitor
(R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-6-carboxamido)propanamido)butylboronic acid	IC50	2.4 nM
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide	KD	2.5 nM
2-(3-CYANO-4-ISOBUTOXY-PHENYL)-4-METHYL-5-THIAZOLE-CARBOXYLIC ACID	IC50	2.9 nM
(1S,3R,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-1,3,25-triol	EC50	3 nM
(2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine	KI	5 nM
1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-((tetrahydro-2-furanyl)carbonyl)piperazine	IC50	5 nM
Staurosporine, 8	IC50	6.5 nM
Atorvastatin lactone	IC50	7 nM
FCE-21336	EC50	13 nM
Amisulpride	KI	13 nM
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide	KI	16 nM
(+/-)-12-Methyl-1,2,3,4,9,13b-hexahydro-2,4a,5-triaza-tribenzo[a,c,e]cycloheptene	KI	18 nM
2-Methyl-butyric acid 8-[2-(4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester((+)-compactin)	IC50	23 nM
(3E)-3-(6H-benzo[c][1]benzoxepin-11-ylidene)-N,N-dimethylpropan-1-amine	KI	25 nM	US-8629135: Pharmaceutical compositions comprising RET inhibitors and methods for the treatment of cancer
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine	KI	25 nM
CS-514	IC50	30 nM
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone	KI	33 nM
(+/-)1-(4-tert-butylphenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-ol	IC50	41 nM
1-(3-chlorophenyl)piperazine	KI	42 nM
5-Chloro-3-(4-methanesulfonyl-phenyl)-6’’-methyl-[2,3’’]bipyridinyl	IC50	70 nM
2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-5-ethyl-4-(2-phenoxyethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one	KI	80 nM
[3-(2-Chloro-phenothiazin-10-yl)-propyl]-dimethyl-amine( Chlorpromazine)	KI	116 nM
APOKYN	KI	117 nM
N-hydroxy-N’-phenyloctanediamide	IC50	140 nM
8-Chloro-11-(4-methyl-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine(Clopazine)	IC50	150 nM
p-aminophenyl sulfone	KI	183 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	190 nM
Urapidil	KI	213 nM
Asendin	KI	221 nM
4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy-benzamide;hydrochloride	IC50	280 nM	US-11147820: Methods for treating GI tract disorders
CHEMBL2074720	IC50	280 nM
NORTRIPTYLINE	KI	294 nM
N,N-dimethyl-2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethanamine	IC50	316 nM
2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one	IC50	330 nM
4-chloro-N-(2-morpholin-4-ylethyl)benzamide	IC50	360 nM
1-Butyl-3-(p-methylphenylsulfonyl)urea	IC50	380 nM
CHEMBL2074750	IC50	400 nM

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 1190 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	decreases reaction, increases response to substance, decreases response to substance, increases expression, decreases expression (+4 more)	20
verlukast	decreases reaction, increases export, increases transport, affects cotreatment, increases uptake (+4 more)	13
estradiol-17 beta-glucuronide	increases uptake, increases reaction, decreases activity, affects localization, decreases reaction (+4 more)	11
sodium arsenite	increases abundance, increases expression, increases reaction, decreases response to substance, affects expression	10
Cyclosporine	decreases reaction, increases transport, decreases activity, affects transport, increases abundance (+3 more)	10
Methotrexate	affects metabolic processing, decreases response to substance, decreases reaction, increases expression, affects response to substance (+4 more)	9
Rifampin	affects export, affects cotreatment, increases expression	9
Acetaminophen	affects activity, increases transport, affects cotreatment, decreases expression, increases expression	7
5(6)-carboxy-2’,7’-dichlorofluorescein	increases uptake, increases export, increases reaction, decreases reaction, increases transport (+1 more)	6
Probenecid	decreases reaction, increases export, affects transport, increases reaction, decreases response to substance (+2 more)	6
sulforaphane	increases expression	5
ochratoxin A	affects export, affects transport, decreases reaction, decreases expression, decreases activity (+1 more)	5
calcein AM	affects transport, increases export, increases transport, decreases reaction, increases expression	5
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	5
Indomethacin	increases abundance, affects export, affects transport, increases reaction, decreases activity (+2 more)	5
Phenobarbital	affects expression, increases expression	5
Resveratrol	affects binding, increases reaction, increases expression, decreases expression, affects export (+1 more)	4
Arsenic Trioxide	decreases response to substance, decreases expression, increases expression	4
Adenosine Triphosphate	affects metabolic processing, affects activity, increases transport, affects reaction, affects cotreatment (+2 more)	4
Lithocholic Acid	increases expression, decreases activity, increases abundance, decreases expression, increases activity	4
Mercury	increases transport, affects reaction, affects abundance, affects response to substance, affects cotreatment (+1 more)	4
Aflatoxin B1	decreases methylation, decreases reaction, affects expression, affects cotreatment, decreases expression (+1 more)	4
Paclitaxel	affects response to substance, affects transport, decreases response to substance, increases export, decreases reaction (+2 more)	4
Leukotriene C4	affects transport, decreases reaction, increases transport	4
beta-Naphthoflavone	increases expression	4
Genistein	increases expression, affects export, affects binding, increases reaction, increases activity (+1 more)	4
bisphenol A	affects expression, affects methylation, affects cotreatment, increases methylation, increases expression	3
fluorexon	affects transport, increases abundance, decreases reaction, affects export	3
arsenite	affects transport, increases expression, increases abundance, decreases reaction, affects reaction (+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)

Via MONDO — disease-level, not drug-specific.

28 trials:

NCT	Phase	Status	Title
NCT05832580	Phase 3	RECRUITING	The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum
NCT01525875	Phase 2	COMPLETED	Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)
NCT02537054	Phase 2	COMPLETED	Intravitreal Aflibercept for Therapy of Patients With Pseudoxanthoma Elasticum (PXE)
NCT04441671	Phase 2	WITHDRAWN	Oral Pyrophosphate Absorption in PXE Disease
NCT05569252	Phase 2	COMPLETED	A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
NCT06462547	Phase 2	ACTIVE_NOT_RECRUITING	ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency
NCT05734196	Phase 1	ACTIVE_NOT_RECRUITING	The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
NCT00470977	Phase 1/2	COMPLETED	Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy
NCT05030831	Phase 1/2	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
NCT07745179	Not specified	COMPLETED	Natural History Study: ENPP1 Deficiency or the Early-Onset Form of ABCC6 Deficiency

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ABCC2 across ~30M SureChEMBL compounds — explore on Sugi Predict.