ABCC8

Summary

ABCC8 (ATP binding cassette subfamily C member 8, HGNC:59) is a protein-coding gene on chromosome 11p15.1, encoding ATP-binding cassette sub-family C member 8 (Q09428). Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release.

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 functions as a modulator of ATP-sensitive potassium channels and insulin release. Mutations in the ABCC8 gene and deficiencies in the encoded protein have been observed in patients with hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high insulin secretion. Mutations have also been associated with non-insulin-dependent diabetes mellitus type II, an autosomal dominant disease of defective insulin secretion. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6833 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperinsulinism (Definitive, ClinGen) — +18 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 2,979 total — 187 pathogenic, 219 likely-pathogenic
• Phenotypes (HPO): 130
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:59
Approved symbol	ABCC8
Name	ATP binding cassette subfamily C member 8
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	HI, PHHI, SUR1, MRP8, ABC36, HHF1, TNDM2
Ensembl gene	ENSG00000006071
Ensembl biotype	protein_coding
OMIM	600509
Entrez	6833

Gene structure

Transcript identifiers

Ensembl transcripts: 100 — 48 retained_intron, 39 nonsense_mediated_decay, 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000302539, ENST00000389817, ENST00000524561, ENST00000525022, ENST00000526002, ENST00000526037, ENST00000526168, ENST00000526921, ENST00000527905, ENST00000528202, ENST00000528374, ENST00000529967, ENST00000530147, ENST00000531137, ENST00000531642, ENST00000531891, ENST00000531911, ENST00000532220, ENST00000532728, ENST00000612903, ENST00000635881, ENST00000642271, ENST00000642579, ENST00000642611, ENST00000642902, ENST00000643260, ENST00000643562, ENST00000643925, ENST00000644057, ENST00000644447, ENST00000644472, ENST00000644484, ENST00000644542, ENST00000644649, ENST00000644675, ENST00000644757, ENST00000644772, ENST00000645004, ENST00000645076, ENST00000645417, ENST00000645744, ENST00000645760, ENST00000645884, ENST00000646003, ENST00000646207, ENST00000646276, ENST00000646592, ENST00000646737, ENST00000646902, ENST00000646993, ENST00000647013, ENST00000647015, ENST00000647086, ENST00000647158, ENST00000682051, ENST00000682053, ENST00000682091, ENST00000682110, ENST00000682140, ENST00000682185, ENST00000682199, ENST00000682204, ENST00000682215, ENST00000682288, ENST00000682442, ENST00000682528, ENST00000682673, ENST00000682805, ENST00000682863, ENST00000682965, ENST00000683066, ENST00000683093, ENST00000683136, ENST00000683153, ENST00000683253, ENST00000683365, ENST00000683377, ENST00000683456, ENST00000683522, ENST00000683531, ENST00000683562, ENST00000683693, ENST00000683725, ENST00000683808, ENST00000684010, ENST00000684014, ENST00000684157, ENST00000684221, ENST00000684253, ENST00000684288, ENST00000684313, ENST00000684332, ENST00000684371, ENST00000684404, ENST00000684442, ENST00000684555, ENST00000684571, ENST00000684593, ENST00000684614, ENST00000684711

RefSeq mRNA: 5 — MANE Select: NM_000352 NM_000352, NM_001287174, NM_001351295, NM_001351296, NM_001351297

CCDS: CCDS31437, CCDS73264, CCDS86183, CCDS86184, CCDS86185

Canonical transcript exons

ENST00000389817 — 39 exons

Exon	Start	End
ENSE00000705134	17427867	17427942
ENSE00000705136	17428289	17428405
ENSE00000705141	17430814	17430959
ENSE00000886096	17428565	17428670
ENSE00001481294	17416930	17416962
ENSE00001607229	17395852	17395930
ENSE00001742580	17396916	17397046
ENSE00003463732	17408392	17408517
ENSE00003466753	17412666	17412746
ENSE00003467114	17397684	17397797
ENSE00003467748	17406622	17406788
ENSE00003468461	17461583	17461825
ENSE00003472684	17407354	17407453
ENSE00003479439	17393697	17393759
ENSE00003479873	17442720	17442882
ENSE00003481953	17427049	17427154
ENSE00003487913	17415304	17415339
ENSE00003502552	17453119	17453283
ENSE00003510121	17410516	17410653
ENSE00003516595	17406888	17407129
ENSE00003518799	17474886	17475027
ENSE00003528254	17395172	17395275
ENSE00003531768	17448516	17448671
ENSE00003550237	17463438	17463604
ENSE00003557574	17395610	17395718
ENSE00003558999	17394266	17394399
ENSE00003579358	17470101	17470222
ENSE00003584058	17432204	17432244
ENSE00003599295	17405494	17405563
ENSE00003605921	17460488	17460676
ENSE00003611247	17414512	17414610
ENSE00003636670	17402661	17402753
ENSE00003644708	17413394	17413478
ENSE00003656899	17443178	17443312
ENSE00003669416	17398339	17398441
ENSE00003673102	17397193	17397313
ENSE00003674189	17404512	17404669
ENSE00003899289	17476629	17476845
ENSE00003899547	17392885	17393128

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 98.48.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5964 / max 157.8662, expressed in 280 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118862	1.3233	271
118861	0.1858	78
118860	0.0874	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.97	gold quality
cerebellar hemisphere	UBERON:0002245	97.80	gold quality
cerebellar cortex	UBERON:0002129	97.66	gold quality
cerebellum	UBERON:0002037	96.73	gold quality
adenohypophysis	UBERON:0002196	96.21	gold quality
pituitary gland	UBERON:0000007	94.87	gold quality
right frontal lobe	UBERON:0002810	94.31	gold quality
primary visual cortex	UBERON:0002436	92.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.98	gold quality
cingulate cortex	UBERON:0003027	91.35	gold quality
anterior cingulate cortex	UBERON:0009835	91.32	gold quality
pancreas	UBERON:0001264	90.87	gold quality
middle temporal gyrus	UBERON:0002771	90.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.61	gold quality
sural nerve	UBERON:0015488	90.01	gold quality
body of pancreas	UBERON:0001150	89.97	gold quality
paraflocculus	UBERON:0005351	89.94	gold quality
prefrontal cortex	UBERON:0000451	89.14	gold quality
neocortex	UBERON:0001950	88.97	gold quality
frontal cortex	UBERON:0001870	88.66	gold quality
occipital lobe	UBERON:0002021	88.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.04	gold quality
cerebral cortex	UBERON:0000956	87.72	gold quality
nucleus accumbens	UBERON:0001882	87.56	gold quality
amygdala	UBERON:0001876	87.54	gold quality
brain	UBERON:0000955	87.50	gold quality
central nervous system	UBERON:0001017	87.40	gold quality
caudate nucleus	UBERON:0001873	87.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.33	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	1862.28
E-GEOD-81547	yes	1822.00
E-HCAD-31	yes	35.74
E-GEOD-81608	yes	22.60
E-MTAB-5061	yes	19.12
E-GEOD-83139	yes	13.17
E-ANND-3	yes	12.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, CREM, FOXA2, FOXO3, HIF1A, IRF2, IRF6, JUN, NEUROD1, NEUROG3, NFKB, NFKBIA, NKRF, PAX6, PDX1, SP1, STAT1

miRNA regulators (miRDB)

11 targeting ABCC8, 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-5692A	100.00	74.40	6850
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Assembly limits the pharmacological complexity of ATP-sensitive potassium channels (PMID:11825905)
• Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels. (PMID:11867634)
• implications of SUR1 in the genetic and pathopysiological mechanisms of type 2 diabetes mellitus (PMID:11938023)
• allelic variation in exon 18, insulin secretion and insulin sensitivity in nondiabetic relatives of type 2 diabetic subjects (PMID:12149601)
• ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyperinsulinemic hypoglycemia of infancy and evaluation of different therapeutic measures. Not predictive of response to drugs. (PMID:12199344)
• the MDR-like core of SUR is linked with the K(IR) pore in KATP channels (PMID:12213829)
• down-regulation of this channel may facilitate myometrial function during late pregnancy (PMID:12356945)
• variant is not associated with type 2 diabetes (PMID:12540637)
• SUR1/Kir6.2 gene region contributes to risk of type 2 diabetes and encodes targets for hypoglycemic medications. Link between mechanism of disease and targets for pharmacological treatment. (PMID:15111507)
• Mutations can yield partially functioning channels, including cases of hyperinsulinism that are fully responsive to diazoxide. therapy. (PMID:15562009)
• Seven novel mutations were found in the ABCC8 coding region, one mutation was found in the KCNJ11 coding region, and one novel mutation was found in each of the two promoter regions screened. (PMID:15579781)
• Polymorphisms of SUR1 gene predicted conversion from impaired glucose tolerance to type 2 diabetes, and the effect of these polymorphisms on diabetes risk was additive with E23K polymorphism of Kir6.2 gene. (PMID:15579791)
• inc activates KATP by binding itself to extracellular His-326 and His-332 of the SUR1 subunit. (PMID:15613469)
• Alleles c of SUR1 are significantly increase the susceptibility to gestational diabetes mellitus. (PMID:15840308)
• In conjunction with this PIP2-dependent process, SUR1 also regulates channel activity via a PIP2-independent, but MgADP-dependent process. (PMID:16373383)
• analysis of mutations in Kir6.2 (KCNJ11) and SUR1 (ABCC8), the spectrum of phenotypes, and the implications for treatment when patients are diagnosed with mutations in these genes [review] (PMID:16416420)
• ABCC8 mutations may have a role in Spanish patients with Hyperinsulinism of Infancy (PMID:16429405)
• SUR1 mutations constitute a new genetic aetiology for neonatal diabetes and they act by reducing the K(ATP) channel’s ATP sensitivity (PMID:16613899)
• Dominant mutations in ABCC8 accounted for 12 percent of cases of neonatal diabetes in the study group. Diabetes results when stimulatory action of SUR1 on Kir pore is elevated. (PMID:16885549)
• The polymorphism of SUR1S1369A was associated with the therapeutic efficacy of gliclazide in type 2 diabetes. After gliclazide treatment, there was association between T/G polymorphism and decrease of HbA1c. (PMID:17118480)
• SUR1 exon 16-3 cytosine/thymine polymorphism is a partial determinant of acute hyperglycaemia-cardiovascular risk factor in type 2 diabetes (PMID:17207885)
• Mutation carriers with neonatal diabetes mellitus may be successflly transferred from insulin to sulfonylurea agents. (PMID:17213273)
• An amino acid substitution (L225P) causes permanent neonatal diabetes but does not affect sulofonylurea sensitivity. (PMID:17317760)
• Six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes. (PMID:17389331)
• study has shown that mutations in the KCNJ11 and ABCC8 are a major cause of transient neonatal diabetes mellitus, accounting for 29% of all cases and 89% of non-6q24 transient neonatal diabetes mellitus (PMID:17446535)
• There is no association between the ABCC8 polymorphism gene and the beta-cell function or the prevalence of chronic diabetic complications in obese patients with long-term T2DM, except for brain stroke. (PMID:17516295)
• Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with glucose dependent insulinotropic peptide in K-cells in human ileum tissue (PMID:17535866)
• study identifies a group of congenital hyperinsulinism-causing SUR1 mutations that cause channel biogenesis/trafficking defects (PMID:17575084)
• SUR1 is abundant in pancreatic endocrine granules, where its function remains to be established. (PMID:17593344)
• We present a term large-for-gestation neonate with congenital hyperinsulinism, who was found to have a novel sporadic missense mutation in the ABCC8 gene (PMID:17597441)
• Significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D were found. (PMID:17823772)
• ABCC8 mutations cause PNDM, TNDM or permanent diabetes diagnosed outside the neonatal period. (PMID:17919176)
• Paternal isodisomy of chromosome 11 unmasks a recessively acting gain-of-function mutation in the ABCC8 gene and causes deregulation of imprinted genes and development of neonatal diabetes and hemihypertrophy. (PMID:17942821)
• Genetic mechanism to explain atypical histological diffuse forms of congenital hyperinsulinism due to mutations of ABCC8. (PMID:17942822)
• Oral sulfonylurea therapy is safe and effective in the short term in most patients with diabetes due to SUR1 mutations and may successfully replace treatment with insulin injections. (PMID:18025408)
• The R1380L & R1380C mutations in the ATP binding site enhance the off-rate of P(i), increasing MgATP hydrolysis, resulting in higher K(ATP) currents in pancreatic beta cells, thus reducing insulin secretion and producing diabetes. (PMID:18025464)
• K(IR)6.2-based channels with diabetogenic receptors reveal that MgATP-dependent hyper-stimulation of mutant SUR can compromise the ability of K(ATP) channels to function as metabolic sensors (PMID:18281290)
• Alanine in HI: a silent mutation cries out! (PMID:18290324)
• Long-term follow-up of three patients with persistent hyperinsulinemic hypoglycemia of infancy due to mutations in the ABCC8 gene. (PMID:18339976)
• An ABCC8/SUR1 mutation with relatively minor effects on K(ATP) channel activity and beta-cell glucose sensing causes diabetes in adulthood. (PMID:18346985)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcc8	ENSDARG00000051879
danio_rerio	abcc8b	ENSDARG00000077007
mus_musculus	Abcc8	ENSMUSG00000040136
rattus_norvegicus	Abcc8	ENSRNOG00000021130
drosophila_melanogaster	l(2)03659	FBGN0010549
drosophila_melanogaster	CG7627	FBGN0032026
drosophila_melanogaster	MRP	FBGN0032456
drosophila_melanogaster	CG9270	FBGN0032908
drosophila_melanogaster	CG10505	FBGN0034612
drosophila_melanogaster	Mrp5	FBGN0038740
drosophila_melanogaster	rdog	FBGN0039644
drosophila_melanogaster	CG11898	FBGN0039645
drosophila_melanogaster	CG31792	FBGN0051792
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477

Paralogs (11): CFTR (ENSG00000001626), ABCC2 (ENSG00000023839), 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 8 — Q09428 (reviewed: Q09428)

Alternative names: Sulfonylurea receptor 1

All UniProt accessions (43): Q09428, A0A2R8Y3M7, A0A2R8Y475, A0A2R8Y4V0, A0A2R8Y4Z4, A0A2R8Y5D8, A0A2R8Y5I7, A0A2R8Y5V4, A0A2R8Y5X1, A0A2R8Y605, A0A2R8Y698, A0A2R8Y6B7, A0A2R8Y6I7, A0A2R8Y6Q0, A0A2R8Y775, A0A2R8Y781, A0A2R8Y7I1, A0A2R8YCG4, A0A2R8YD94, A0A2R8YDB5, A0A2R8YDE9, A0A2R8YDG0, A0A2R8YDG6, A0A2R8YDX3, A0A2R8YEE5, A0A2R8YFB3, A0A2R8YFU3, A0A2R8YG67, A0A2R8YGQ6, A0A2R8YHG6, A0A804HI74, A0A804HJG5, A0A804HJH4, A0A804HJZ2, A0A804HK47, A0A804HK92, A0A804HL76, A0A804HLA1, E9PK50, H0YDH8, H0YE33, H0YEA9, H0YF51

UniProt curated annotations — full annotation on UniProt →

Function. Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release. In pancreatic cells, it forms KATP channels with KCNJ11; KCNJ11 forms the channel pore while ABCC8 is required for activation and regulation.

Subunit / interactions. Forms an heterooctamer with KCNJ11; four ABCC8/SUR1 molecules interact with one KCNJ11 homotetramer.

Subcellular location. Cell membrane.

Disease relevance. Leucine-induced hypoglycemia (LIH) [MIM:240800] Rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine. The disease is caused by variants affecting the gene represented in this entry. Hyperinsulinemic hypoglycemia, familial, 1 (HHF1) [MIM:256450] A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF1 is the most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF1 inheritance can be autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Diabetes mellitus, permanent neonatal, 3 (PNDM3) [MIM:618857] A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM3 patients may also have developmental delay, muscle weakness, and epilepsy. PNDM3 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry. Transient neonatal diabetes mellitus 2 (TNDM2) [MIM:610374] Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. Transient neonatal diabetes remits early, with a possible relapse during adolescence. The disease is caused by variants affecting the gene represented in this entry. Maturity-onset diabetes of the young 12 (MODY12) [MIM:621196] A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. KATP channels are regulated by cytoplasmic ATP/ADP ratios; ATP inhibits the channel by closing the pore, while ADP activates the channel. Activated by phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2).

Miscellaneous. Abundant isoform with prodiabetic properties, predominant in heart.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q09428-1	1	yes
Q09428-2	2
Q09428-3	3, SUR1Delta2

RefSeq proteins (5): NP_000343, NP_001274103, NP_001338224, NP_001338225, NP_001338226 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000388	ABCC8/9	Family
IPR000844	ABCC8	Family
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR050173	ABC_transporter_C-like	Family

Pfam: PF00005, PF00664

UniProt features (307 total): sequence variant 116, helix 64, strand 34, turn 22, topological domain 18, transmembrane region 17, binding site 13, sequence conflict 10, domain 4, compositionally biased region 2, glycosylation site 2, splice variant 2, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7S5V	ELECTRON MICROSCOPY	3.3
7S5X	ELECTRON MICROSCOPY	3.7
7S60	ELECTRON MICROSCOPY	3.7
6C3O	ELECTRON MICROSCOPY	3.9
7S5Y	ELECTRON MICROSCOPY	3.9
7S5Z	ELECTRON MICROSCOPY	3.9
7S61	ELECTRON MICROSCOPY	4
6C3P	ELECTRON MICROSCOPY	5.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q09428-F1	82.56	0.42

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 (13): 688; 716; 720; 720; 721; 774; 1380; 1381; 1383; 1384; 1385; 1386 …

Disulfide bonds (1): 6–26

Glycosylation sites (2): 10, 1049

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1296025	ATP sensitive Potassium channels
R-HSA-422356	Regulation of insulin secretion
R-HSA-5683177	Defective ABCC8 can cause hypo- and hyper-glycemias
R-HSA-112316	Neuronal System
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 578 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_MEMORY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_GLUTAMATE_SECRETION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_RESPONSE_TO_ZINC_ION, GOBP_BEHAVIOR, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, PID_HNF3B_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS

GO Biological Process (32): action potential (GO:0001508), intracellular glucose homeostasis (GO:0001678), potassium ion transport (GO:0006813), female pregnancy (GO:0007565), memory (GO:0007613), visual learning (GO:0008542), response to pH (GO:0009268), response to xenobiotic stimulus (GO:0009410), response to zinc ion (GO:0010043), negative regulation of low-density lipoprotein particle clearance (GO:0010989), negative regulation of angiogenesis (GO:0016525), cellular response to nutrient levels (GO:0031669), response to lipopolysaccharide (GO:0032496), positive regulation of tumor necrosis factor production (GO:0032760), response to insulin (GO:0032868), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), positive regulation of potassium ion transport (GO:0043268), negative regulation of insulin secretion (GO:0046676), regulation of insulin secretion (GO:0050796), neuromuscular process (GO:0050905), transmembrane transport (GO:0055085), negative regulation of glial cell proliferation (GO:0060253), glutamate secretion, neurotransmission (GO:0061535), negative regulation of neuroblast migration (GO:0061855), potassium ion transmembrane transport (GO:0071805), obsolete inorganic cation transmembrane transport (GO:0098662), positive regulation of uterine smooth muscle relaxation (GO:1900721), positive regulation of tight junction disassembly (GO:1905075), negative regulation of blood-brain barrier permeability (GO:1905604), potassium ion import across plasma membrane (GO:1990573), response to ATP (GO:0033198), negative regulation of neurogenesis (GO:0050768)

GO Molecular Function (13): potassium channel activity (GO:0005267), ATP binding (GO:0005524), sulfonylurea receptor activity (GO:0008281), ATP-activated inward rectifier potassium channel activity (GO:0015272), ATP hydrolysis activity (GO:0016887), ATPase-coupled monoatomic cation transmembrane transporter activity (GO:0019829), ADP binding (GO:0043531), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (8): plasma membrane (GO:0005886), inward rectifying potassium channel (GO:0008282), synaptic vesicle membrane (GO:0030672), potassium ion-transporting ATPase complex (GO:0031004), sarcolemma (GO:0042383), presynaptic membrane (GO:0042734), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Inwardly rectifying K+ channels	1
Integration of energy metabolism	1
ABC transporter disorders	1
Potassium Channels	1
Neuronal System	1
Metabolism	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
insulin secretion	2
adenyl ribonucleotide binding	2
ATPase-coupled transmembrane transporter activity	2
regulation of membrane potential	1
glucose homeostasis	1
intracellular chemical homeostasis	1
metal ion transport	1
multi-organism reproductive process	1
multi-multicellular organism process	1
learning or memory	1
visual behavior	1
associative learning	1
response to abiotic stimulus	1
response to chemical	1
response to metal ion	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
response to nutrient levels	1
cellular response to stimulus	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
response to peptide hormone	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
potassium ion transport	1
regulation of potassium ion transport	1
positive regulation of monoatomic ion transport	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
regulation of protein secretion	1

Protein interactions and networks

STRING

2810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC8	KCNJ11	Q14654	999
ABCC8	KCNJ8	Q15842	998
ABCC8	TRPM4	Q8TD43	992
ABCC8	GCK	P35557	944
ABCC8	INS	P01308	897
ABCC8	RAPGEF4	Q8WZA2	868
ABCC8	ENSA	O43768	822
ABCC8	HNF1A	P20823	819
ABCC8	GCG	P01275	817
ABCC8	SLC2A2	P11168	801
ABCC8	PAX4	O43316	765
ABCC8	WFS1	O76024	733
ABCC8	SLC30A8	Q8IWU4	717
ABCC8	PDX1	P52945	698
ABCC8	FOXA2	Q9Y261	697

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ABCC8	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
ABCC8	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
KCNJ11	ABCC8	psi-mi:“MI:0407”(direct interaction)	0.360
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
ABCC8	ABCC9	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): ABCC8 (Affinity Capture-RNA), RAPGEF4 (Affinity Capture-Western), KCNJ11 (Affinity Capture-Western), ABCC8 (Proximity Label-MS), ABCC8 (Two-hybrid), ABCC8 (Affinity Capture-MS), ABCC8 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), ABCC9 (Affinity Capture-MS), ABCC8 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, B2RX12, E9PU17, E9PX95, F1MWM0, O00329, O15438, O35600, O75899, O88563, O88871, O94911, O95477, P41233, P55205, P58428, P78363, Q09427, Q09428, Q09429, Q2NKY8, Q5BJS0, Q5R607, Q5ZI74, Q6TL19, Q7L2E3, Q7TNJ2, Q80T41, Q84M24, Q8CF82, Q8IUA7, Q8K440, Q8K441, Q8K442, Q8K448, Q8K449, Q8LPK0, Q8N139, Q8NCL4, Q8R420

Diamond homologs: A0A0D1CZ63, A0A1U8QTJ9, A2XCD4, A7KVC2, B2RX12, E9Q236, F1M3J4, F9X9V4, G4N2B5, G5EFD4, J9VQH1, J9VWU3, O15438, O15439, O15440, O35379, O88563, O95255, P08716, P0C086, P0C087, P0CE69, P0CL92, P0CL93, P10089, P14772, P16532, P21441, P23702, P26760, P32386, P33527, P38735, P39109, P53049, P55122, P55469, P9WEL8, Q02592, Q04473

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ABCC8	“form complex”	“KATP channel”	binding
RAPGEF4	“up-regulates quantity”	ABCC8	binding
PKA	“down-regulates activity”	ABCC8	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

2979 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	187
Likely pathogenic	219
Uncertain significance	812
Likely benign	1177
Benign	81

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065615	NM_000352.6(ABCC8):c.4369G>A (p.Ala1457Thr)	Pathogenic
1069205	NM_000352.6(ABCC8):c.1617T>A (p.Tyr539Ter)	Pathogenic
1069965	NM_000352.6(ABCC8):c.2117-3_2117-2inv	Pathogenic
1071327	NM_000352.6(ABCC8):c.148+1del	Pathogenic
1072639	NM_000352.6(ABCC8):c.333del (p.Met112fs)	Pathogenic
1072767	NM_000352.6(ABCC8):c.790C>T (p.Gln264Ter)	Pathogenic
1073214	NM_000352.6(ABCC8):c.428G>A (p.Trp143Ter)	Pathogenic
1073392	NM_000352.6(ABCC8):c.8del (p.Leu3fs)	Pathogenic
1073510	NM_000352.6(ABCC8):c.2113C>T (p.Arg705Ter)	Pathogenic
1179142	NM_000352.6(ABCC8):c.1893del (p.Gln632fs)	Pathogenic
1216356	NM_000352.6(ABCC8):c.4370C>T (p.Ala1457Val)	Pathogenic
1315564	NM_000352.6(ABCC8):c.985A>T (p.Lys329Ter)	Pathogenic
1338427	NM_000352.3:c.85_1011+8del	Pathogenic
1338472	NM_000352.6(ABCC8):c.2473C>T (p.Arg825Trp)	Pathogenic
1338474	NM_000352.6(ABCC8):c.4515C>G (p.Asp1505Glu)	Pathogenic
1338516	NM_000352.6(ABCC8):c.4608+1G>A	Pathogenic
1338602	NM_000352.6(ABCC8):c.1011+1G>T	Pathogenic
1346183	NM_000352.6(ABCC8):c.4532T>A (p.Ile1511Asn)	Pathogenic
1353831	NM_000352.6(ABCC8):c.1553del (p.Phe518fs)	Pathogenic
1368654	NM_000352.6(ABCC8):c.1369G>T (p.Gly457Ter)	Pathogenic
1371056	NM_000352.6(ABCC8):c.2266G>T (p.Glu756Ter)	Pathogenic
1374172	NM_000352.6(ABCC8):c.3952del (p.Leu1317_Leu1318insTer)	Pathogenic
1377688	NM_000352.6(ABCC8):c.643del (p.Val215fs)	Pathogenic
1382227	NC_000011.9:g.(?17414433)(17438525_?)del	Pathogenic
1392912	NC_000011.9:g.(?17464257)(17474840_?)del	Pathogenic
1427394	NM_000352.6(ABCC8):c.4545+1del	Pathogenic
1430334	NM_000352.6(ABCC8):c.76del (p.Cys26fs)	Pathogenic
1438638	NM_000352.6(ABCC8):c.863G>A (p.Trp288Ter)	Pathogenic
1443398	NM_000352.6(ABCC8):c.3966_3972del (p.Glu1323fs)	Pathogenic
1445163	NM_000352.6(ABCC8):c.4588del (p.Arg1530fs)	Pathogenic

SpliceAI

6977 predictions. Top by Δscore:

Variant	Effect	Δscore
11:17393124:CGATG:C	acceptor_gain	1.0000
11:17394263:AAC:A	donor_loss	1.0000
11:17394264:A:AC	donor_gain	1.0000
11:17394264:A:T	donor_loss	1.0000
11:17394265:C:CC	donor_gain	1.0000
11:17394265:C:CG	donor_loss	1.0000
11:17394297:T:TA	donor_gain	1.0000
11:17394319:T:TA	donor_gain	1.0000
11:17394395:GGCAT:G	acceptor_gain	1.0000
11:17394396:GCAT:G	acceptor_gain	1.0000
11:17394397:CAT:C	acceptor_gain	1.0000
11:17394397:CATC:C	acceptor_gain	1.0000
11:17394398:AT:A	acceptor_gain	1.0000
11:17394398:ATC:A	acceptor_loss	1.0000
11:17394400:C:CC	acceptor_gain	1.0000
11:17394407:C:CT	acceptor_gain	1.0000
11:17394408:A:T	acceptor_gain	1.0000
11:17394412:C:CT	acceptor_gain	1.0000
11:17394412:C:T	acceptor_gain	1.0000
11:17394413:G:T	acceptor_gain	1.0000
11:17395179:T:TA	donor_gain	1.0000
11:17395729:CCCAG:C	acceptor_gain	1.0000
11:17395730:CCAG:C	acceptor_gain	1.0000
11:17395731:C:T	acceptor_gain	1.0000
11:17395731:CAG:C	acceptor_gain	1.0000
11:17395732:A:T	acceptor_gain	1.0000
11:17395739:G:GC	acceptor_gain	1.0000
11:17396911:CTGA:C	donor_loss	1.0000
11:17396912:TGACC:T	donor_loss	1.0000
11:17396913:GAC:G	donor_loss	1.0000

AlphaMissense

10334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:17394336:G:T	A1492D	1.000
11:17394339:A:G	L1491P	1.000
11:17394348:A:G	L1488P	1.000
11:17394365:G:C	S1482R	1.000
11:17394365:G:T	S1482R	1.000
11:17394367:T:G	S1482R	1.000
11:17395207:A:G	L1459P	1.000
11:17395222:A:G	L1454P	1.000
11:17395267:A:G	L1439P	1.000
11:17395269:G:C	N1438K	1.000
11:17395269:G:T	N1438K	1.000
11:17413449:A:G	L807P	1.000
11:17393124:C:G	R1538P	0.999
11:17393128:G:C	H1537D	0.999
11:17393707:A:T	V1533D	0.999
11:17393724:G:C	F1527L	0.999
11:17393724:G:T	F1527L	0.999
11:17393726:A:G	F1527L	0.999
11:17393749:A:G	L1519P	0.999
11:17394276:T:A	D1512V	0.999
11:17394291:G:T	A1507D	0.999
11:17394292:C:G	A1507P	0.999
11:17394293:C:A	E1506D	0.999
11:17394293:C:G	E1506D	0.999
11:17394294:T:A	E1506V	0.999
11:17394294:T:C	E1506G	0.999
11:17394294:T:G	E1506A	0.999
11:17394295:C:G	E1506Q	0.999
11:17394295:C:T	E1506K	0.999
11:17394297:T:A	D1505V	0.999

dbSNP variants (sampled 300 via entrez): RS1000034444 (11:17401723 G>A,C), RS1000052282 (11:17424620 G>A), RS1000069692 (11:17441707 C>A), RS1000169405 (11:17474199 C>A), RS1000179036 (11:17474325 T>C), RS1000218088 (11:17435207 C>T), RS1000232637 (11:17396293 G>A), RS1000257802 (11:17394946 G>A,T), RS1000325701 (11:17478641 T>C), RS1000330638 (11:17434782 A>G), RS1000331952 (11:17412447 T>C), RS1000335332 (11:17429418 G>C), RS1000343470 (11:17406358 G>A,T), RS1000385430 (11:17468870 C>A,T), RS1000428318 (11:17401373 A>C)

Disease associations

OMIM: gene MIM:600509 | disease phenotypes: MIM:256450, MIM:125850, MIM:606391, MIM:125853, MIM:240800, MIM:610374, MIM:618857, MIM:621196, MIM:606176, MIM:108800

GenCC curated gene-disease

Disease	Classification	Inheritance
diabetes mellitus	Definitive	Semidominant
hyperinsulinemic hypoglycemia, familial, 1	Definitive	Autosomal dominant
diabetes mellitus, permanent neonatal 3	Definitive	Semidominant
familial hyperinsulinism	Definitive	Autosomal recessive
transient neonatal diabetes mellitus	Strong	Autosomal dominant
permanent neonatal diabetes mellitus	Strong	Autosomal recessive
diabetes mellitus, noninsulin-dependent	Strong	Autosomal dominant
hypoglycemia, leucine-induced	Strong	Autosomal dominant
diabetes mellitus, transient neonatal, 2	Strong	Unknown
maturity-onset diabetes of the young	Strong	Autosomal dominant
pulmonary arterial hypertension	Strong	Autosomal dominant
neonatal diabetes mellitus	Strong	Semidominant
autosomal dominant hyperinsulinism due to SUR1 deficiency	Supportive	Autosomal dominant
diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency	Supportive	Autosomal dominant
DEND syndrome	Supportive	Autosomal dominant
autosomal recessive hyperinsulinism due to SUR1 deficiency	Supportive	Autosomal recessive
type 2 diabetes mellitus	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (4)

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

Disease	Classification	Inheritance
pulmonary arterial hypertension	Moderate	AD
hyperinsulinism	Definitive	AD
hyperinsulinemic hypoglycemia, familial, 1	Definitive	AR
monogenic diabetes	Definitive	SD

Mondo (27): hyperinsulinemic hypoglycemia, familial, 1 (MONDO:0009734), maturity-onset diabetes of the young (MONDO:0018911), transient neonatal diabetes mellitus (MONDO:0020525), type 2 diabetes mellitus (MONDO:0005148), hypoglycemia, leucine-induced (MONDO:0009415), diabetes mellitus, transient neonatal, 2 (MONDO:0012480), diabetes mellitus, permanent neonatal 3 (MONDO:0030088), neonatal diabetes mellitus (MONDO:0016391), familial hyperinsulinism (MONDO:0017182), maturity-onset diabetes of the young, type 12 (MONDO:0978299), permanent neonatal diabetes mellitus (MONDO:0100164), pulmonary arterial hypertension (MONDO:0015924), diabetes mellitus (MONDO:0005015), brain edema (MONDO:0006684), hyperinsulinism (MONDO:0002177)

Orphanet (12): Autosomal dominant hyperinsulinism due to SUR1 deficiency (Orphanet:276575), Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency (Orphanet:276598), MODY (Orphanet:552), Transient neonatal diabetes mellitus (Orphanet:99886), Neonatal diabetes mellitus (Orphanet:224), Familial hyperinsulinism (Orphanet:276525), Isolated permanent neonatal diabetes mellitus (Orphanet:99885), Pulmonary arterial hypertension (Orphanet:182090), Rare genetic diabetes mellitus (Orphanet:183625), Congenital isolated hyperinsulinism (Orphanet:657), Interatrial communication (Orphanet:1478), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422)

HPO phenotypes

130 total (30 of 130 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000079	Abnormality of the urinary system
HP:0000103	Polyuria
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000124	Renal tubular dysfunction
HP:0000158	Macroglossia
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000707	Abnormality of the nervous system
HP:0000713	Agitation
HP:0000737	Irritability
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000842	Hyperinsulinemia
HP:0000855	Insulin resistance
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0000980	Pallor
HP:0001069	Episodic hyperhidrosis
HP:0001249	Intellectual disability
HP:0001250	Seizure

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001356_14	Gout	1.000000e-07
GCST001356_15	Gout	1.000000e-07
GCST005440_1	Alcohol dependence symptom count	9.000000e-06
GCST005951_67	Body mass index	6.000000e-09
GCST005951_68	Body mass index	3.000000e-09
GCST006231_47	Mean arterial pressure	4.000000e-09
GCST007517_16	Type 2 diabetes	4.000000e-17
GCST007518_20	Type 2 diabetes (adjusted for BMI)	5.000000e-22
GCST009391_164	Metabolite levels	7.000000e-06
GCST010118_122	Type 2 diabetes	2.000000e-26
GCST010272_12	Circulating leptin levels or type 2 diabetes	2.000000e-12
GCST011358_7	Academic attainment (English)	7.000000e-06
GCST012053_1	Weight	9.000000e-07
GCST90000025_197	Appendicular lean mass	1.000000e-16

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007835	alcohol dependence measurement
EFO:0004340	body mass index
EFO:0006340	mean arterial pressure
EFO:0010487	glutamate measurement
EFO:0005000	leptin measurement
EFO:0011015	educational attainment
EFO:0004338	body weight
EFO:0004980	appendicular lean mass

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D001929	Brain Edema	C10.228.140.187
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D030342	Genetic Diseases, Inborn	C16.320
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D006946	Hyperinsulinism	C18.452.394.968
D007003	Hypoglycemia	C18.452.394.984
D006831	Polyhydramnios	C12.050.703.610
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)
C563672	Diabetes Mellitus, Transient Neonatal, 2 (supp.)
C537150	Hypoglycemia, leucine-induced (supp.)
C562772	Mason-Type Diabetes (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2071 (SINGLE PROTEIN), CHEMBL2095152 (PROTEIN COMPLEX GROUP), CHEMBL2096972 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 114,982 (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
CHEMBL1272	REPAGLINIDE	4	33,453
CHEMBL181	DIAZOXIDE	4	27,974
CHEMBL472	GLYBURIDE	4	53,236
CHEMBL49035	CROMAKALIM	2	135
CHEMBL12531	CLAMIKALANT	2	80
CHEMBL135191	TIFENAZOXIDE	2	104

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs757110	Efficacy	3	sulfonamides;urea derivatives	Diabetes Mellitus

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5219	ABCC8, KCNJ11	3	3.75	6	repaglinide;metformin;sulfonamides;urea derivatives;tacrolimus;gliclazide;sulfonamides
rs757110	ABCC8, KCNJ11	3	0.75	1	sulfonamides;urea derivatives
rs2237991	ABCC8		0.00	0
rs2074315	ABCC8		0.00	0
rs1799857	ABCC8		0.00	0
rs1799854	ABCC8		0.00	0
rs1799859	ABCC8		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
repaglinide	Inhibition	6.97	pIC50

ChEMBL bioactivities

376 potent at pChembl≥5 of 416 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.42	Kd	0.38	nM	CHEMBL3330880
9.27	EC50	0.537	nM	CHEMBL321455
8.68	Kd	2.08	nM	CHEMBL3330879
8.52	IC50	3	nM	CHEMBL134168
8.37	IC50	4.3	nM	GLYBURIDE
8.30	EC50	5.012	nM	CHEMBL3138573
8.30	EC50	5.012	nM	CHEMBL2111694
8.20	EC50	6.31	nM	CHEMBL323159
8.06	EC50	8.71	nM	CHEMBL3392139
8.05	EC50	8.913	nM	CHEMBL50760
7.95	EC50	11.22	nM	CHEMBL2111694
7.90	EC50	12.59	nM	CHEMBL3138553
7.89	EC50	12.88	nM	CHEMBL108723
7.85	EC50	14.13	nM	CHEMBL108251
7.70	IC50	20	nM	CROMAKALIM
7.66	EC50	21.88	nM	CHEMBL11458
7.66	EC50	21.88	nM	CHEMBL3138587
7.65	EC50	22.39	nM	CHEMBL107888
7.64	EC50	22.91	nM	CHEMBL3138607
7.63	EC50	23.44	nM	CHEMBL110399
7.59	EC50	25.7	nM	CHEMBL3138549
7.59	EC50	25.7	nM	CHEMBL2112487
7.57	EC50	26.92	nM	CHEMBL320983
7.56	EC50	27.54	nM	CHEMBL108586
7.55	EC50	28.18	nM	CHEMBL3138545
7.52	EC50	30	nM	CHEMBL36665
7.52	EC50	30	nM	CHEMBL34523
7.51	EC50	30.9	nM	CHEMBL3138586
7.50	EC50	31.62	nM	CHEMBL321210
7.49	EC50	32.36	nM	CHEMBL320518
7.48	EC50	33.11	nM	CHEMBL3138586
7.46	EC50	35	nM	CHEMBL37534
7.46	EC50	34.67	nM	(-)-CROMAKALIM
7.45	EC50	35.48	nM	CHEMBL108440
7.42	EC50	38.02	nM	CHEMBL3138561
7.40	EC50	40	nM	CHEMBL35356
7.36	EC50	43.65	nM	CHEMBL3138553
7.36	IC50	44	nM	CHEMBL143181
7.35	EC50	44.67	nM	CHEMBL11458
7.31	EC50	48.98	nM	CHEMBL49153
7.30	Kd	50	nM	REPAGLINIDE
7.28	EC50	52.48	nM	CHEMBL3138560
7.28	EC50	52.48	nM	CHEMBL300958
7.27	EC50	53.7	nM	CHEMBL3138606
7.27	EC50	53.7	nM	CHEMBL3138579
7.26	EC50	54.95	nM	CHEMBL3138596
7.20	EC50	63.1	nM	CHEMBL109412
7.20	EC50	63.1	nM	CHEMBL110399
7.19	EC50	64.57	nM	CHEMBL110511
7.17	EC50	67.61	nM	CHEMBL323787

PubChem BioAssay actives

375 with measured affinity, of 906 total; 50 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
4-acetamido-5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide	1163348: Binding affinity to SUR1 (unknown origin)	kd	0.0004	uM
9-(3-bromo-4-fluorophenyl)-5,13-dithia-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0005	uM
5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxy-4-[[2-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyacetyl]amino]benzamide	1163348: Binding affinity to SUR1 (unknown origin)	kd	0.0021	uM
6-chloro-N-(1-methylcyclobutyl)-1,1-dioxo-4H-thieno[3,2-e][1,2,4]thiadiazin-3-imine	208994: Inhibition of [3H]glibenclamide binding to HEK293 cells co-expressing human Sulfonylurea receptor SUR1 and Inward rectifier K+ channel Kir6.2 at high affinity state with 2 mM MgATP	ic50	0.0030	uM
glyburide	201322: Inhibition of human SUR1/Kir6.2 expressed in CHO cells	ic50	0.0043	uM
(8R)-8-(3-bromo-4-fluorophenyl)-6,6-dioxo-12-oxa-6lambda6-thia-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-dien-10-one	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0050	uM
(8S)-8-(3-bromo-4-fluorophenyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93985: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0050	uM
(9S)-9-(3-bromo-4-fluorophenyl)-3,4,5,6,7,9-hexahydrofuro[3,4-b]quinoline-1,8-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0063	uM
8-(3-bromo-4-fluorophenyl)-10,10-dioxo-5-oxa-10lambda6-thia-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-dien-6-one	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0087	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]propanamide	159672: Potent effective concentration was evaluated for KATP channel opening activity in pig bladder strips	ec50	0.0089	uM
(9R)-9-(3-bromo-4-fluorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93984: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0126	uM
8-(3-bromo-4-fluorophenyl)-5-methyl-12-oxa-2,5-diazatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0129	uM
8-(3-bromo-4-fluorophenyl)-5,11-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0141	uM
3-hydroxy-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromene-6-carbonitrile	78296: Contraction and relaxation of guinea pig portal vein with KCl and glibenclamide respectively	ic50	0.0200	uM
(9S)-9-(3-iodo-4-methylphenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0219	uM
1-cyano-2-(2-methylbutan-2-yl)-3-pyridin-3-ylguanidine	93984: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0219	uM
(8S)-8-(3-bromo-4-fluorophenyl)-5-oxa-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0224	uM
(9S)-9-(3-bromo-4-fluorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93984: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0229	uM
8-(3-bromo-4-fluorophenyl)-5,11-dioxa-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-6,10-dione	93985: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0234	uM
(8R)-8-(3-bromo-4-fluorophenyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0257	uM
(9S)-9-(3-bromo-4-chlorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0257	uM
9-(3-bromo-4-fluorophenyl)-5,13-dioxa-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0269	uM
7-(3-bromo-4-fluorophenyl)-5-methyl-1,1-dioxo-2,3,4,7-tetrahydrothieno[3,2-b]pyridine-6-carbonitrile	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0275	uM
(9S)-9-(4-fluoro-3-iodophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0282	uM
9-(3-bromo-4-fluorophenyl)-5,6,7,9-tetrahydro-4H-pyrazolo[5,1-b]quinazolin-8-one	73908: Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	ec50	0.0300	uM
9-(4-bromo-3-fluorophenyl)-5,6,7,9-tetrahydro-4H-pyrazolo[5,1-b]quinazolin-8-one	73908: Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	ec50	0.0300	uM
(8R)-8-(3-bromo-4-fluorophenyl)-6,6-dioxo-6lambda6-thia-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-dien-10-one	93977: Evaluated for K-ATP activity in terms of stable twitch response through field-stimulated landrace pig detrusor assay	ec50	0.0309	uM
8-(3-bromo-4-fluorophenyl)-12-oxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0316	uM
(9R)-9-(3-bromo-4-fluorophenyl)-3,4,5,6,7,9-hexahydrofuro[3,4-b]quinoline-1,8-dione	93985: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0324	uM
(3R,4S)-3-hydroxy-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromene-6-carbonitrile	93984: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0347	uM
9-(3-bromo-4-fluorophenyl)-7,7-dimethyl-4,4a,5,6,8a,9-hexahydropyrazolo[5,1-b]quinazolin-8-one	73908: Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	ec50	0.0350	uM
5-(3-bromo-4-fluorophenyl)-1,5,7,8,9,10-hexahydropyrano[3,4-b]quinoline-4,6-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0355	uM
10-(3-bromo-4-fluorophenyl)-1,1-dioxo-2,3,4,5,6,7,8,10-octahydrothiopyrano[3,2-b]quinolin-9-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0380	uM
8-(3-bromo-4-fluorophenyl)-12-thia-2,6,7-triazatricyclo[7.4.0.03,7]trideca-3,5-dien-10-one	73908: Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	ec50	0.0400	uM
N-[4-(benzenesulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide	78296: Contraction and relaxation of guinea pig portal vein with KCl and glibenclamide respectively	ic50	0.0440	uM
(E)-N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]but-2-enamide	159672: Potent effective concentration was evaluated for KATP channel opening activity in pig bladder strips	ec50	0.0490	uM
Repaglinide	238081: Displacement of [3H]glibenclamide from COS-1 cells expressing Sulfonylurea receptor 1 (SUR-1)	kd	0.0500	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]-3-methylbenzamide	159672: Potent effective concentration was evaluated for KATP channel opening activity in pig bladder strips	ec50	0.0525	uM
(8R)-8-(3-bromo-4-fluorophenyl)-10,10-dioxo-10lambda6-thia-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-dien-6-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0525	uM
9-(3-bromo-4-fluorophenyl)-11,11-dioxo-5-oxa-11lambda6-thia-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-dien-7-one	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0537	uM
methyl 7-(3-bromo-4-fluorophenyl)-5-methyl-1,1-dioxo-2,3,4,7-tetrahydrothieno[3,2-b]pyridine-6-carboxylate	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0537	uM
(9S)-9-(3,4-dibromophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0549	uM
9-(3-bromo-4-fluorophenyl)-5-oxa-13-thia-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0631	uM
8-(3-bromo-4-fluorophenyl)-5-oxa-12-thia-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0646	uM
8-(3-bromo-4-fluorophenyl)-11-oxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0676	uM
3-(2,4-dinitrophenyl)-4-nitro-5-(trifluoromethyl)-1H-pyrazole	95325: Maximum activation of human KATP (SUR1/Kir6.2) channel expressed in Xenopus oocytes	ec50	0.0700	uM
8-(3-bromo-4-fluorophenyl)-10,10-dioxo-5-oxa-10lambda6-thia-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-dien-6-one	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0724	uM
10-(3-bromo-4-fluorophenyl)-4,5,6,7,8,10-hexahydro-3H-pyrano[4,3-b]quinoline-1,9-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0794	uM
6-chloro-N-cyclobutyl-1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-3-imine	444907: Activation of human recombinant SUR1/Kir6.2 channel expressed in HEK293 cells assessed as increase in ionic current by whole cell patch clamp assay	ec50	0.0800	uM
6-chloro-1,1-dioxo-N-(2-phenylpropan-2-yl)-4H-thieno[3,2-e][1,2,4]thiadiazin-3-imine	267953: Displacement of [3H]glibenclamide from human Kir6.2/SUR1 expressed in HEK293 cells in presence of 2 mM ATP	ic50	0.0810	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tolbutamide	affects cotreatment, decreases response to substance, increases activity, decreases reaction, increases secretion	3
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
uranyl acetate	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
manganese chloride	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
beryllium fluoride	decreases activity	1
glimepiride	affects cotreatment, decreases response to substance	1
mitiglinide	affects cotreatment, increases response to substance	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
imeglimin	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Chlorpropamide	affects cotreatment, decreases response to substance	1
Cisplatin	affects response to substance	1
Diethylhexyl Phthalate	decreases expression	1
Gliclazide	affects cotreatment, increases response to substance	1
Manganese	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Uranium	affects expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Mifepristone	decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

84 unique, capped per target: 52 functional, 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3385406	Binding	Binding affinity to SUR1 (unknown origin)	Novel sulfonyl(thio)urea derivatives act efficiently both as insulin secretagogues and as insulinomimetic compounds. — Eur J Med Chem
CHEMBL868372	Functional	Reduction of blood glucose level in alloxan induced diabetic mice at 200 mg/kg	Synthesis and antihyperglycemic evaluation of various protoberberine derivatives. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 2 embryonic stem cell, 2 somatic stem cell, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4GR	Abcc8-A4	Embryonic stem cell	Male
CVCL_A4GW	Abcc8-A2	Embryonic stem cell	Male
CVCL_B3MQ	CHIpMSC1	Somatic stem cell	Male
CVCL_B3MR	CHIpMSC3	Somatic stem cell	Male
CVCL_LB87	NISK9	Spontaneously immortalized cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00044746	PHASE4	COMPLETED	Study Evaluating the Safety and Efficacy of Piperacillin/Tazobactam and Ampicillin/Sulbactam in Patients With Diabetic Foot Infections
NCT00069602	PHASE4	COMPLETED	Assessing Continuous Glucose Monitors in Healthy Children
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00108615	PHASE4	COMPLETED	Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
NCT00117780	PHASE4	COMPLETED	Comparison of Insulin Detemir Given Once or Twice Daily in Type 1 Diabetes
NCT00120341	PHASE4	COMPLETED	Anodyne Therapy in Diabetic Sensory Neuropathy
NCT00121355	PHASE4	COMPLETED	Novofine Autocover Safety Needle Versus BD Safety Glide
NCT00135226	PHASE4	ACTIVE_NOT_RECRUITING	ASCEND: A Study of Cardiovascular Events iN Diabetes
NCT00144937	PHASE4	UNKNOWN	Multifactorial Intervention on Cardiovascular Risk Factors in Subjects With Peripheral Arterial Disease
NCT00147251	PHASE4	COMPLETED	Stop Atherosclerosis in Native Diabetics Study
NCT00157638	PHASE4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00162344	PHASE4	COMPLETED	A Study of Stress Heart Imaging in Patients With Diabetes at Risk for Coronary Disease.
NCT00177138	PHASE4	TERMINATED	Use of Campath for Induction and Maintenance Therapy in Pancreas After Kidney Transplantation
NCT00182494	PHASE4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00202618	PHASE4	UNKNOWN	Rationale and Design for Shiga Microalbuminuria Reduction Trial
NCT00209170	PHASE4	COMPLETED	Depression-Diabetes Mechanisms: Urban African Americans
NCT00209417	PHASE4	TERMINATED	Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Computed Tomography
NCT00212004	PHASE4	TERMINATED	Pioglitazone Protects Diabetes Mellitus (DM) Patients Against Re-Infarction (PPAR Study)
NCT00219440	PHASE4	COMPLETED	A Portion-controlled Diet Will Prevent Weight Gain in Diabetics Treated With ACTOS
NCT00225849	PHASE4	UNKNOWN	Japanese Primary Prevention Project With Aspirin
NCT00231894	PHASE4	COMPLETED	Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
NCT00234871	PHASE4	COMPLETED	Tarka® vs. Lotrel® in Hypertensive, Diabetic Subjects With Renal Disease (TANDEM)
NCT00235014	PHASE4	COMPLETED	A Study for Prevention of Kidney Disease in Diabetic Patients (BENEDICT)
NCT00236379	PHASE4	COMPLETED	A Study of the Effects of Risperidone and Olanzapine on Blood Glucose (Sugar) in Patients With Schizophrenia or Schizoaffective Disorder
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00263393	PHASE4	COMPLETED	Rural Andhra Pradesh Cardiovascular Prevention Study (RAPCAPS)
NCT00264901	PHASE4	COMPLETED	Comparison of Self Adjustment Versus Standard of Care Treatment in Subjects With Type 2 Diabetes
NCT00274274	PHASE4	COMPLETED	Efficacy and Safety of a Fixed or a Flexible Supplementary Insulin Therapy in Type 2 Diabetes
NCT00282451	PHASE4	COMPLETED	Effect of Biphasic Insulin Compared to Biphasic Insulin Combined With Insulin Aspart, With or Without Metformin in Type 2 Diabetes
NCT00282659	PHASE4	COMPLETED	The Use of Magnesium to Improve Blood Pressure, Cholesterol, and Glucose Control
NCT00287820	PHASE4	COMPLETED	Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism
NCT00295555	PHASE4	COMPLETED	Doxazosin Effects on ABPM in Hypertensive Patients With Diabetic Nephropathy
NCT00299169	PHASE4	TERMINATED	Randomized Trial Comparing N of 1 Trials to Standard Practice to Improve Adherence to Statins in Patients With Diabetes
NCT00301392	PHASE4	COMPLETED	Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)
NCT00306696	PHASE4	COMPLETED	Examining the Effect of Different Diuretics on Fluid Retention in Diabetics Treated With Rosiglitazone.
NCT00309465	PHASE4	COMPLETED	Perioperative Insulin Glargine Dosing Study