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): 3,035 total — 188 pathogenic, 223 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 42 tissues, sQTL in 10 (q < 0.05)
• Phenotypes (HPO): 130
• Drug target: yes — 13 via a complex or family; 6 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 10 — Acetohexamide, Chlorpropamide, Gliclazide, +7 more (Sulfonylurea receptor 1, Kir6.2)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_000352
• Interaction hub: 1,746 STRING partners (top 10% of genes corpus-wide)

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: 103 — 48 retained_intron, 40 nonsense_mediated_decay, 14 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000389817 · MANE Plus Clinical: ENST00000302539

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 6, TSL 5: 10

ENST00000389817, ENST00000302539, 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, ENST00001023200, ENST00001137625, ENST00001137626

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.

Highest expression (Bgee): islet of Langerhans, hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ABCC8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 42 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 52 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.6e-100	+1.20	11:17476510:G:A
Muscle Skeletal	eqtl	1.0e-88	+0.95	11:17476510:G:A
Skin Sun Exposed Lower leg	eqtl	1.3e-63	+0.87	11:17476510:G:A
Artery Aorta	eqtl	5.7e-61	+1.24	11:17476510:G:A
Artery Tibial	eqtl	2.7e-57	+0.83	11:17476510:G:A
Skin Not Sun Exposed Suprapubic	eqtl	6.4e-49	+0.80	11:17476510:G:A
Heart Atrial Appendage	eqtl	4.4e-41	+0.64	11:17476247:C:G
Nerve Tibial	eqtl	1.9e-38	+0.34	11:17476247:C:G
Brain Cerebellum	eqtl	3.0e-38	+0.73	11:17401860:GT:G
Adipose Subcutaneous	eqtl	2.0e-37	+0.70	11:17476510:G:A
Heart Left Ventricle	eqtl	5.6e-37	+0.55	11:17476247:C:G
Artery Coronary	eqtl	1.0e-27	+1.10	11:17476510:G:A
Brain Cerebellar Hemisphere	eqtl	1.5e-25	+0.53	11:17393230:AG:A
Adipose Visceral Omentum	eqtl	5.1e-24	+0.60	11:17476510:G:A
Brain Hypothalamus	eqtl	2.2e-23	+0.48	11:17476247:C:G
Brain Putamen basal ganglia	eqtl	4.1e-22	+0.45	11:17476247:C:G
Brain Caudate basal ganglia	eqtl	2.3e-20	+0.41	11:17476247:C:G
Breast Mammary Tissue	eqtl	4.2e-20	+0.29	11:17476247:C:G
Brain Nucleus accumbens basal ganglia	eqtl	1.0e-19	+0.54	11:17476247:C:G
Brain Frontal Cortex BA9	eqtl	1.7e-19	+0.39	11:17393230:AG:A

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

showing 100 of 289 tissues 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
forebrain	UBERON:0001890	87.13	gold quality
telencephalon	UBERON:0001893	86.94	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.31	gold quality
putamen	UBERON:0001874	85.94	gold quality
Ammon’s horn	UBERON:0001954	85.89	gold quality
frontal pole	UBERON:0002795	85.22	gold quality
superior frontal gyrus	UBERON:0002661	85.11	gold quality
spinal cord	UBERON:0002240	84.92	gold quality
temporal lobe	UBERON:0001871	84.37	gold quality
postcentral gyrus	UBERON:0002581	84.09	gold quality
hypothalamus	UBERON:0001898	83.38	gold quality
right lung	UBERON:0002167	83.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.17	gold quality
cerebellar vermis	UBERON:0004720	83.03	gold quality
parietal lobe	UBERON:0001872	82.69	gold quality
cortical plate	UBERON:0005343	81.77	gold quality
body of stomach	UBERON:0001161	81.55	gold quality
orbitofrontal cortex	UBERON:0004167	80.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.62	gold quality
middle frontal gyrus	UBERON:0002702	80.29	gold quality
entorhinal cortex	UBERON:0002728	79.50	gold quality
substantia nigra	UBERON:0002038	79.44	gold quality
upper lobe of left lung	UBERON:0008952	78.98	gold quality
stomach	UBERON:0000945	78.27	gold quality
right lobe of thyroid gland	UBERON:0001119	78.20	gold quality
midbrain	UBERON:0001891	78.12	gold quality
left lobe of thyroid gland	UBERON:0001120	78.07	gold quality
fundus of stomach	UBERON:0001160	77.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.46	gold quality
thyroid gland	UBERON:0002046	76.31	gold quality
seminal vesicle	UBERON:0000998	76.28	gold quality
endothelial cell	CL:0000115	75.87	gold quality
upper lobe of lung	UBERON:0008948	75.86	gold quality
pons	UBERON:0000988	75.71	gold quality
ganglionic eminence	UBERON:0004023	75.50	gold quality
ventricular zone	UBERON:0003053	75.48	gold quality
type B pancreatic cell	CL:0000169	74.95	gold quality
endocervix	UBERON:0000458	74.45	gold quality
tibial nerve	UBERON:0001323	73.71	gold quality
gastrocnemius	UBERON:0001388	73.00	gold quality
inferior olivary complex	UBERON:0002127	72.56	silver quality
CA1 field of hippocampus	UBERON:0003881	72.50	silver quality
lateral nuclear group of thalamus	UBERON:0002736	72.40	gold quality
ectocervix	UBERON:0012249	72.36	gold quality
heart left ventricle	UBERON:0002084	72.19	gold quality
apex of heart	UBERON:0002098	72.06	gold quality
muscle of leg	UBERON:0001383	71.87	gold quality
cardiac ventricle	UBERON:0002082	71.69	gold quality
right atrium auricular region	UBERON:0006631	71.21	gold quality
cardiac atrium	UBERON:0002081	70.52	gold quality
corpus callosum	UBERON:0002336	70.50	gold quality
prostate gland	UBERON:0002367	70.28	gold quality
lateral globus pallidus	UBERON:0002476	70.01	gold quality
substantia nigra pars compacta	UBERON:0001965	69.63	silver quality
body of uterus	UBERON:0009853	69.46	gold quality
embryo	UBERON:0000922	68.53	gold quality
mucosa of transverse colon	UBERON:0004991	68.52	gold quality
heart	UBERON:0000948	68.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	68.17	gold quality
muscle organ	UBERON:0001630	68.13	gold quality
olfactory bulb	UBERON:0002264	68.13	gold quality
skeletal muscle organ	UBERON:0014892	68.13	gold quality
right adrenal gland	UBERON:0001233	68.04	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	67.69	gold quality
medulla oblongata	UBERON:0001896	67.38	silver quality
transverse colon	UBERON:0001157	67.15	gold quality
small intestine	UBERON:0002108	67.00	gold quality
diaphragm	UBERON:0001103	66.22	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 66 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	34.1	medium
Somatosensory cortex	tissue	34.1
Occipital cortex	tissue	33.6
Pituitary gland	tissue	23.3
Motor cortex	tissue	18.5
Retrosplenial and cingulate cortex	tissue	18.5
Hippocampal formation	tissue	17.4
Entorhinal cortex	tissue	17.4
Prefrontal cortex	tissue	16.8
Temporal cortex	tissue	15.9
Retrosplenial cortex	tissue	15.8
Insular cortex	tissue	15.4
Postcentral gyrus	tissue	10.2
Pancreas	tissue	10.1	medium
Frontal cortex	tissue	9.9
Putamen	tissue	8.5
Basal ganglia	tissue	8.4	medium
Spinal cord	tissue	8.1
Locus coeruleus	tissue	7.7
Hippocampus	tissue	7.7	low
Cerebellum	tissue	7.3	high
Thalamus	tissue	5.9
Ventral forebrain	tissue	5.9
Nucleus accumbens	tissue	5.5
Olfactory bulb	tissue	5.4
Pons	tissue	5.1
Amygdala	tissue	5.0
Superior colliculi	tissue	5.0
Caudate putamen	tissue	5.0
Medulla oblongata	tissue	4.3
Midbrain	tissue	4.2
Hypothalamus	tissue	4.2
Choroid plexus	tissue	3.8
Substantia nigra	tissue	3.6
Septum	tissue	3.5
Periaqueductal gray	tissue	3.4
Corpus callosum	tissue	2.1
Adrenal gland	tissue	1.8	medium
Retina	tissue	1.2
Thyroid gland	tissue	1.2	low
Breast	tissue	1.0	low
Heart muscle	tissue	1.0	not detected
Stomach 1	tissue	0.9	low
Seminal vesicle	tissue	0.7	low
Epididymis	tissue	0.7	low
Vagina	tissue	0.6	not detected
Tongue	tissue	0.5
Prostate	tissue	0.4	low
Cervix	tissue	0.3	low
Skeletal muscle	tissue	0.3	not detected
Endometrium 1	tissue	0.3	low
Adipose tissue	tissue	0.2	not detected
Smooth muscle	tissue	0.2	not detected
Small intestine	tissue	0.2	low
Skin 1	tissue	0.1	not detected
Testis	tissue	0.1	not detected
Rectum	tissue	0.1	low
Parathyroid gland	tissue	0.1	low
Colon	tissue	0.1	low
Placenta	tissue	0.1	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Precentral gyrus (10.5), Parietal operculum (9.9), Posterior insular cortex (9.7), Claustrum (9.2), Parieto-insular cortex (8.9).

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)

Targeting ABCC8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

11 miRNAs:

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

gnomAD constraint: pLI 9.53e-33, LOEUF 0.829, missense Z 2.85 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000389817 — one region, missense o/e 0.84. 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1352629) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired glucose tolerance	4
decreased insulin secretion	3
hypoglycemia	2
increased circulating glucose level	2
decreased circulating glucose level	2
increased insulin secretion	1
abnormal insulin secretion	1
increased lean body mass	1
abnormal pancreatic beta cell morphology	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
Glarea lozoyensis ATCC 20868	S3D778	51.9%	Diamond
Pyricularia oryzae 70-15	G4N2B5	47.9%	Diamond
Aspergillus nidulans FGSC A4	A0A1U8QTJ9	40.6%	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
USH1C	protein-coding	10083
NCR3LG1	protein-coding	374383
KCNJ11	protein-coding	3767
LINC02729	ncRNA	102723330
OTOG	protein-coding	340990
NUCB2	protein-coding	4925
MYOD1	protein-coding	4654

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 (309 total): sequence variant 116, helix 66, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7S5V	Human KATP channel in open conformation, focused on SUR	ELECTRON MICROSCOPY	3.3
7S5X	Human KATP channel in open conformation, focused on Kir and one SUR, position 1	ELECTRON MICROSCOPY	3.7
7S60	Human KATP channel in open conformation, focused on Kir and one SUR, position 4	ELECTRON MICROSCOPY	3.7
6C3O	Cryo-EM structure of human KATP bound to ATP and ADP in quatrefoil form	ELECTRON MICROSCOPY	3.9
7S5Y	Human KATP channel in open conformation, focused on Kir and one SUR, position 2	ELECTRON MICROSCOPY	3.9
7S5Z	Human KATP channel in open conformation, focused on Kir and one SUR, position 3	ELECTRON MICROSCOPY	3.9
7S61	Human KATP channel in open conformation, focused on Kir and one SUR, position 5	ELECTRON MICROSCOPY	4
6C3P	Cryo-EM structure of human KATP bound to ATP and ADP in propeller form	ELECTRON MICROSCOPY	5.6

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Metabolic proteins, Transporters, Primary Active Transporters, Predicted membrane proteins, Plasma proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Other congenital disorders of metabolism, Diabetes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoli; cytosol; principal piece

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
688	ATP
716	ATP
720	ATP
720	Mg(2+)
721	ATP
774	Mg(2+)
1380	ADP
1381	ADP
1383	ADP
1384	ADP
1385	ADP
1386	ADP
1482	ATP

Disulfide bonds (1)

Type	Positions
Disulfide bond	6–26

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	10, 1049

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

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

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 (27): 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), 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), transmembrane transport (GO:0055085), negative regulation of glial cell proliferation (GO:0060253), negative regulation of neuroblast migration (GO:0061855), potassium ion transmembrane transport (GO:0071805), 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

8 top-level categories:

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

showing 60 of 76 GO namespaces:

Category	Terms
insulin secretion	2
adenyl ribonucleotide binding	2
anion binding	2
ATPase-coupled transmembrane transporter activity	2
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 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
regulation of peptide hormone secretion	1
transport	1
cellular process	1
negative regulation of cell population proliferation	1
glial cell proliferation	1
negative regulation of gliogenesis	1
regulation of glial cell proliferation	1
negative regulation of cell migration	1
regulation of neuroblast migration	1
neuroblast migration	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
purine ribonucleoside triphosphate binding	1
transmembrane signaling receptor activity	1
inward rectifier potassium channel activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
monoatomic cation transmembrane transporter activity	1
active monoatomic ion transmembrane transporter activity	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 48 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
inward rectifying potassium channel	CC	direct assay
ATPase-coupled monoatomic cation transmembrane transporter activity	MF	direct assay
potassium channel activity	MF	mutant phenotype
transmembrane transporter binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,746 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC8	KCNJ11	Q14654	997
ABCC8	KCNJ8	Q15842	889
ABCC8	INS	P01308	888
ABCC8	GCK	P35557	869
ABCC8	KCNA3	P22001	819
ABCC8	HNF1A	P20823	819
ABCC8	GCG	P01275	813
ABCC8	SLC2A2	P11168	792
ABCC8	PAX4	O43316	778
ABCC8	TRPM4	Q8TD43	750
ABCC8	WFS1	O76024	739
ABCC8	SLC30A8	Q8IWU4	731
ABCC8	PDX1	P52945	692
ABCC8	ZFP57	Q9NU63	683
ABCC8	NEUROD1	Q13562	668

IntAct

Human interaction partners of ABCC8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
HMGA1	physical association	0.400	1
F2RL1	physical association	0.370	1
KCNJ11	direct interaction	0.360	1
ABCC9	association	0.350	1

BioGRID (12 interactions; top human partners by supporting records): ABCC9 (Affinity Capture-MS), F2RL1 (Two-hybrid), HNRNPL (Affinity Capture-RNA), INS (Affinity Capture-MS), KCNJ11 (Affinity Capture-Western), KIF14 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), PARP12 (Proximity Label-MS), PARP4 (Proximity Label-MS), PARP9 (Proximity Label-MS), RAPGEF4 (Affinity Capture-Western), SCN2A (Affinity Capture-MS)

SIGNOR signaling

showing 3 of 4 signaling interactions:

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

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ ABCC8-RAPGEF4 complex	2	ABCC8, RAPGEF4
★ KCNJ11-ABCC8 complex	2	ABCC8, KCNJ11

Disease & clinical

Genetic variants

Variant evidence for ABCC8: 3,035 ClinVar records (411 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 14 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

3,035 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	188
Likely pathogenic	223
Uncertain significance	847
Likely benign	1186
Benign	72

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 411 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
9088	NM_000352.6(ABCC8):c.3989-9G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	23
196880	NM_000352.6(ABCC8):c.4160_4162del (p.Phe1387del)	Pathogenic	criteria provided, multiple submitters, no conflicts	18
9096	NM_000352.6(ABCC8):c.4477C>T (p.Arg1493Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
434056	NM_000352.6(ABCC8):c.1792C>T (p.Arg598Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
9086	NM_000352.6(ABCC8):c.4307G>A (p.Arg1436Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
9097	NM_000352.6(ABCC8):c.4516G>A (p.Glu1506Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
370909	NM_000352.6(ABCC8):c.1879del (p.His627fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
446765	NM_000352.6(ABCC8):c.1634del (p.Phe545fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
585351	NM_000352.6(ABCC8):c.742C>T (p.Arg248Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
434053	NM_000352.6(ABCC8):c.2992C>T (p.Arg998Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
235633	NM_000352.6(ABCC8):c.3640C>T (p.Arg1214Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
280115	NM_000352.6(ABCC8):c.3130_3149del (p.Thr1044fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
370163	NM_000352.6(ABCC8):c.3748C>T (p.Arg1250Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
370210	NM_000352.6(ABCC8):c.3574del (p.Asp1192fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
370604	NM_000352.6(ABCC8):c.1630+1G>T	Pathogenic	criteria provided, multiple submitters, no conflicts	7

Per-variant reference — Sugi Variant

Explore ABCC8’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; 33 predictions of 3,865):

Position(s)	Effect	Δscore	Sites
11:17394264–17394265	donor_loss	1.0000	2
11:17394400–17394401	acceptor_loss	1.0000	5
11:17394408	acceptor_gain	1.0000
11:17394412–17394413	acceptor_gain	1.0000	2
11:17395731–17395732	acceptor_gain	1.0000	2
11:17396914–17396915	donor_loss	1.0000	5
11:17397191–17397192	donor_loss	1.0000	5
11:17397209	donor_gain	1.0000
11:17402659–17402660	donor_loss	1.0000	5
11:17402754–17402755	acceptor_loss	1.0000	5

AlphaMissense

4,908 missense substitutions predicted likely pathogenic (of 10,334 scored), across 1,180 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
M730	9	0.927	0.994
M441	9	0.867	0.996
M931	9	0.848	0.974
D860	8	0.998	0.999
D1505	8	0.998	0.999
D853	8	0.997	0.999
D1512	8	0.997	0.999
D854	8	0.994	0.999
D810	8	0.993	0.998
S1482	8	0.993	1.000
H1537	8	0.992	0.999
F1527	8	0.990	0.999
N786	8	0.989	0.999
F577	8	0.987	0.999
D1030	8	0.987	0.996
D209	8	0.983	0.994
D310	8	0.982	0.995
D1132	8	0.981	0.991
D1440	8	0.980	0.995
D29	8	0.979	0.994

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Pancreatic Adenocarcinoma)

Disease associations

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

GenCC curated gene-disease

18 curated gene-disease records:

Disease	Classification	Inheritance	Records
diabetes mellitus	Definitive	Semidominant
hyperinsulinemic hypoglycemia, familial, 1	Definitive	Autosomal dominant	9
diabetes mellitus, permanent neonatal 3	Definitive	Semidominant	4
hypoglycemia, leucine-induced	Definitive	Autosomal dominant	3
familial hyperinsulinism	Definitive	Autosomal recessive
monogenic diabetes	Definitive	Semidominant
transient neonatal diabetes mellitus	Strong	Autosomal dominant	2
permanent neonatal diabetes mellitus	Strong	Autosomal recessive	2
diabetes mellitus, noninsulin-dependent	Strong	Autosomal dominant
diabetes mellitus, transient neonatal, 2	Strong	Unknown	2
maturity-onset diabetes of the young	Strong	Autosomal dominant	2
pulmonary arterial hypertension	Strong	Autosomal dominant	2
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

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

4 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
Congenital hyperinsulinism	green
Diabetes with additional phenotypes suggestive of a monogenic aetiology	green
Familial diabetes	green
Monogenic diabetes	green
Neonatal diabetes	green
Neonatal diabetes - small panel	green
Pulmonary arterial hypertension	green

Mondo (23): hyperinsulinemic hypoglycemia, familial, 1 (MONDO:0009734), type 2 diabetes mellitus (MONDO:0005148), neonatal diabetes mellitus (MONDO:0016391), familial hyperinsulinism (MONDO:0017182), maturity-onset diabetes of the young (MONDO:0018911), hypoglycemia, leucine-induced (MONDO:0009415), diabetes mellitus, transient neonatal, 2 (MONDO:0012480), diabetes mellitus, permanent neonatal 3 (MONDO:0030088), permanent neonatal diabetes mellitus (MONDO:0100164), maturity-onset diabetes of the young, type 12 (MONDO:0978299), autosomal dominant hyperinsulinism due to SUR1 deficiency (MONDO:0017184), monogenic diabetes (MONDO:0015967), hypoglycemia (MONDO:0004946), congestive heart failure (MONDO:0005009), atrial septal defect (MONDO:0006664), transient neonatal diabetes mellitus (MONDO:0020525), DEND syndrome (MONDO:0019207), intermediate DEND syndrome (MONDO:0020569), diabetes mellitus (MONDO:0005015), (MONDO:0007455), diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency (MONDO:0017187), autosomal recessive hyperinsulinism due to SUR1 deficiency (MONDO:0019333), pulmonary arterial hypertension (MONDO:0015924)

Orphanet (11): Autosomal dominant hyperinsulinism due to SUR1 deficiency (Orphanet:276575), Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency (Orphanet:276598), Neonatal diabetes mellitus (Orphanet:224), Familial hyperinsulinism (Orphanet:276525), MODY (Orphanet:552), Transient neonatal diabetes mellitus (Orphanet:99886), Isolated permanent neonatal diabetes mellitus (Orphanet:99885), Rare genetic diabetes mellitus (Orphanet:183625), Interatrial communication (Orphanet:1478), DEND syndrome (Orphanet:79134), Intermediate DEND syndrome (Orphanet:99989)

HPO phenotypes

showing 60 of 130 phenotypes (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
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001271	Polyneuropathy
HP:0001279	Syncope
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001325	Hypoglycemic coma
HP:0001347	Hyperreflexia
HP:0001488	Bilateral ptosis
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001518	Small for gestational age
HP:0001520	Large for gestational age
HP:0001537	Umbilical hernia
HP:0001627	Abnormal heart morphology
HP:0001639	Hypertrophic cardiomyopathy
HP:0001649	Tachycardia
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss
HP:0001943	Hypoglycemia
HP:0001944	Dehydration
HP:0001952	Glucose intolerance
HP:0001953	Diabetic ketoacidosis
HP:0001959	Polydipsia

GWAS associations

14 associations:

Study	Trait	p-value
GCST010118_164	Type 2 diabetes	2e-26
GCST007518_20	Type 2 diabetes (adjusted for BMI)	5e-22
GCST007517_17	Type 2 diabetes	4e-17
GCST90000025_609	Appendicular lean mass	1e-16
GCST010272_12	Circulating leptin levels or type 2 diabetes	2e-12
GCST005951_78	Body mass index	3e-9
GCST006231_14	Mean arterial pressure	4e-9
GCST005951_77	Body mass index	6e-9
GCST001356_3	Gout	1e-7
GCST001356_4	Gout	1e-7
GCST012053_2	Weight	9e-7
GCST009391_142	Metabolite levels	7e-6
GCST011358_11	Academic attainment (English)	7e-6
GCST005440_1	Alcohol dependence symptom count	9e-6

EFO canonical traits (from GWAS)

8 canonical traits:

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

9 disease descriptors:

Descriptor	Name	Tree numbers
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D007003	Hypoglycemia	C18.452.394.984
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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ABCC8 — the drug acts on the assembly or class, not necessarily on this subunit alone.

13 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ACETOHEXAMIDE	Sulfonylurea receptor 1, Kir6.2	2	4
CHLORPROPAMIDE	Sulfonylurea receptor 1, Kir6.2	2	4
GLICLAZIDE	Sulfonylurea receptor 1, Kir6.2	2	4
GLIMEPIRIDE	Sulfonylurea receptor 1, Kir6.2	2	4
GLIPIZIDE	Sulfonylurea receptor 1, Kir6.2	2	4
GLYBURIDE	Sulfonylurea receptor 1, Kir6.2	2	4
NATEGLINIDE	Sulfonylurea receptor 1, Kir6.2	2	4
REPAGLINIDE	Sulfonylurea receptor 1, Kir6.2	2	4
TOLAZAMIDE	Sulfonylurea receptor 1, Kir6.2	2	4
TOLBUTAMIDE	Sulfonylurea receptor 1, Kir6.2	2	4
MITIGLINIDE	Sulfonylurea receptor 1, Kir6.2	2	3
NAMINIDIL	Sulfonylurea receptors; K-ATP channels	4	2
SARAKALIM	Sulfonylurea receptors; K-ATP channels	4	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 115,810 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

6 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL181	DIAZOXIDE	4	28,185
CHEMBL472	GLYBURIDE	4	53,640
CHEMBL1272	REPAGLINIDE	4	33,658
CHEMBL12531	CLAMIKALANT	2	80
CHEMBL49035	CROMAKALIM	2	136
CHEMBL135191	TIFENAZOXIDE	2	111

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

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

PharmGKB variants

2 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

PharmGKB variant annotations

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

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs757110	sulfonamides, urea derivatives	Efficacy	Genotypes AA + CC is associated with increased response to sulfonamides, urea derivatives in people with Diabetes Mellitus as compared to genotype AC.	PMID:29681852
rs757110	gliclazide, glyburide	Efficacy	Genotype CC is associated with increased likelihood of treatment failure when treated with glibenclamide or gliclazide in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + AC.	PMID:32468916
rs5219	“““metformin””, ““sulfonamides, urea derivatives”””	Efficacy	Genotypes CT + TT is associated with increased clinical benefit to metformin and sulfonamides, urea derivatives in people with Diabetes Mellitus, Type 2 as compared to genotype CC.	PMID:39005567

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

Binding affinities (BindingDB)

34 measured of 44 human assays (47 total across all organisms); most potent 34 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3330880	KD	0.38 nM
CHEMBL3330879	KD	2.1 nM
3-(2,4-Dinitro-phenyl)-4-nitro-5-trifluoromethyl-1H-pyrazole	EC50	70 nM
CHEMBL568795	EC50	80 nM
(2-Chloro-7,7-dioxo-4,7-dihydro-1,7lambda*6*-dithia-4,6-diaza-inden-5-yl)-cyclobutyl-amine	IC50	120 nM
6-bromo-3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide	EC50	160 nM
2-Methoxy-4-{[(S)-3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid	IC50	163 nM
(2-Chloro-7,7-dioxo-4,7-dihydro-1,7lambda*6*-dithia-4,6-diaza-inden-5-yl)-(1,1-dimethyl-propyl)-amine	IC50	180 nM
6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide	EC50	180 nM
(2-Chloro-7,7-dioxo-4,7-dihydro-1,7-dithia-4,6-diaza-inden-5-yl)-(1-methyl-cyclopropyl)-amine	EC50	190 nM
(7-Chloro-1,1-dioxo-1,4-dihydro-1lambda*6*-benzo[1,2,4]thiadiazin-3-yl)-cyclobutyl-amine]	EC50	196 nM
2-(2-Fluoro-ethoxy)-4-{[(S)-3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid	IC50	281 nM
Cyclobutyl-(7-fluoro-1,1-dioxo-1,4-dihydro-1lambda*6*-benzo[1,2,4]thiadiazin-3-yl)-amine	EC50	356 nM
Cyclobutyl-(7-nitro-1,1-dioxo-1,4-dihydro-1lambda*6*-benzo[1,2,4]thiadiazin-3-yl)-amine	EC50	530 nM
6-chloro-3-{[1-(trifluoromethyl)cyclopropyl]-amino}-4H-thieno[3,2-e]-1,2,4-thiadiazine1,1-dioxide	EC50	530 nM
3-(2,4-Bis-trifluoromethyl-phenyl)-4-nitro-5-trifluoromethyl-1H-pyrazole	EC50	540 nM
4-Nitro-3-(4-nitro-phenyl)-5-trifluoromethyl-1H-pyrazole	EC50	700 nM
6-chloro-3-(1-phenylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine1,1-dioxide	EC50	810 nM
3-(2,4-Difluoro-phenyl)-4-nitro-5-trifluoromethyl-1H-pyrazole	EC50	1150 nM
Cyclobutyl-(1,1-dioxo-1,4-dihydro-1lambda*6*-benzo[1,2,4]thiadiazin-3-yl)-amine	EC50	1960 nM
(2-Chloro-7,7-dioxo-4,7-dihydro-1,7lambda*6*-dithia-4,6-diaza-inden-5-yl)-propyl-amine	IC50	2270 nM
Cyclobutyl-(7-methoxy-1,1-dioxo-1,4-dihydro-1lambda*6*-benzo[1,2,4]thiadiazin-3-yl)-amine	EC50	3870 nM
CHEMBL5290652	EC50	7420 nM
5-[2-(5-chloro-2-methoxybenzamido)ethyl]-2-methoxy-benzenesulfonyl-3-methlthiourea	IC50	8200 nM
6-chloro-3-(1-methylcyclobutyl)-amino-4H-thieno[3,2-e]-1,2,4-thiadiazine1,1-dioxide	IC50	10800 nM
4-amino-6-methoxy-2-(trifluoromethyl)quinoline-3-carbonitrile	EC50	15000 nM
[(2Z)-4-(4-fluorophenyl)-2-[(4-fluorophenyl)imino]-1,3-thiazol-3(2H)-yl]ethanol	EC50	21000 nM
NSC_3019	EC50	23500 nM
4-Nitro-3-phenyl-5-trifluoromethyl-1H-pyrazole	EC50	30000 nM
N*3*-Cyclobutyl-1,1-dioxo-1,4-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-3,7-diamine	EC50	31000 nM
AGEE-623ZW	IC50	72300 nM
(2-Chloro-7,7-dioxo-4,7-dihydro-1,7lambda*6*-dithia-4,6-diaza-inden-5-yl)-isopropyl-amine	IC50	187000 nM
CHEMBL2111887	IC50	224000 nM
tert-Butyl-(2-chloro-7,7-dioxo-4,7-dihydro-1,7lambda*6*-dithia-4,6-diaza-inden-5-yl)-amine	IC50	1.35e+06 nM

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

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

Chemical	Actions (top 5)	PubMed papers
Tolbutamide	decreases reaction, increases secretion, affects cotreatment, decreases response to substance, increases activity	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	decreases response to substance, affects cotreatment	1
Cisplatin	affects response to substance	1
Dieldrin	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Gliclazide	affects cotreatment, increases response to substance	1
Heptachlor	decreases expression	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

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)

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

showing 60 of 562 trials:

NCT	Phase	Status	Title
NCT00044746	Phase 4	COMPLETED	Study Evaluating the Safety and Efficacy of Piperacillin/Tazobactam and Ampicillin/Sulbactam in Patients With Diabetic Foot Infections
NCT00069602	Phase 4	COMPLETED	Assessing Continuous Glucose Monitors in Healthy Children
NCT00079638	Phase 4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00095446	Phase 4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	Phase 4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00108615	Phase 4	COMPLETED	Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance
NCT00117780	Phase 4	COMPLETED	Comparison of Insulin Detemir Given Once or Twice Daily in Type 1 Diabetes
NCT00120341	Phase 4	COMPLETED	Anodyne Therapy in Diabetic Sensory Neuropathy
NCT00121355	Phase 4	COMPLETED	Novofine Autocover Safety Needle Versus BD Safety Glide
NCT00135226	Phase 4	ACTIVE_NOT_RECRUITING	ASCEND: A Study of Cardiovascular Events iN Diabetes
NCT00144937	Phase 4	UNKNOWN	Multifactorial Intervention on Cardiovascular Risk Factors in Subjects With Peripheral Arterial Disease
NCT00147251	Phase 4	COMPLETED	Stop Atherosclerosis in Native Diabetics Study
NCT00157638	Phase 4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00162344	Phase 4	COMPLETED	A Study of Stress Heart Imaging in Patients With Diabetes at Risk for Coronary Disease.
NCT00177138	Phase 4	TERMINATED	Use of Campath for Induction and Maintenance Therapy in Pancreas After Kidney Transplantation
NCT00182494	Phase 4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
NCT00184561	Phase 4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	Phase 4	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	Phase 4	UNKNOWN	Rationale and Design for Shiga Microalbuminuria Reduction Trial
NCT00209170	Phase 4	COMPLETED	Depression-Diabetes Mechanisms: Urban African Americans
NCT00209417	Phase 4	TERMINATED	Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Computed Tomography
NCT00212004	Phase 4	TERMINATED	Pioglitazone Protects Diabetes Mellitus (DM) Patients Against Re-Infarction (PPAR Study)
NCT00219440	Phase 4	COMPLETED	A Portion-controlled Diet Will Prevent Weight Gain in Diabetics Treated With ACTOS
NCT00225849	Phase 4	UNKNOWN	Japanese Primary Prevention Project With Aspirin
NCT00231894	Phase 4	COMPLETED	Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
NCT00234871	Phase 4	COMPLETED	Tarka® vs. Lotrel® in Hypertensive, Diabetic Subjects With Renal Disease (TANDEM)
NCT00235014	Phase 4	COMPLETED	A Study for Prevention of Kidney Disease in Diabetic Patients (BENEDICT)
NCT00236379	Phase 4	COMPLETED	A Study of the Effects of Risperidone and Olanzapine on Blood Glucose (Sugar) in Patients With Schizophrenia or Schizoaffective Disorder
NCT00241904	Phase 4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00263393	Phase 4	COMPLETED	Rural Andhra Pradesh Cardiovascular Prevention Study (RAPCAPS)
NCT00264901	Phase 4	COMPLETED	Comparison of Self Adjustment Versus Standard of Care Treatment in Subjects With Type 2 Diabetes
NCT00274274	Phase 4	COMPLETED	Efficacy and Safety of a Fixed or a Flexible Supplementary Insulin Therapy in Type 2 Diabetes
NCT00282451	Phase 4	COMPLETED	Effect of Biphasic Insulin Compared to Biphasic Insulin Combined With Insulin Aspart, With or Without Metformin in Type 2 Diabetes
NCT00282659	Phase 4	COMPLETED	The Use of Magnesium to Improve Blood Pressure, Cholesterol, and Glucose Control
NCT00287820	Phase 4	COMPLETED	Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism
NCT00295555	Phase 4	COMPLETED	Doxazosin Effects on ABPM in Hypertensive Patients With Diabetic Nephropathy
NCT00299169	Phase 4	TERMINATED	Randomized Trial Comparing N of 1 Trials to Standard Practice to Improve Adherence to Statins in Patients With Diabetes
NCT00301392	Phase 4	COMPLETED	Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)
NCT00306696	Phase 4	COMPLETED	Examining the Effect of Different Diuretics on Fluid Retention in Diabetics Treated With Rosiglitazone.
NCT00309465	Phase 4	COMPLETED	Perioperative Insulin Glargine Dosing Study
NCT00313742	Phase 4	COMPLETED	The Effect of Exercise on Blood Glucose Levels in Patients With Type 1 Diabetes: A Comparison of 3 Long-acting Insulins
NCT00322075	Phase 4	COMPLETED	LANCGMS - Lantus Continuous Glucose Monitoring Subcutaneous
NCT00327912	Phase 4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00335101	Phase 4	WITHDRAWN	Renal Effects of Three Iodinated Contrast Media (CM) in Patients at Risk Undergoing Coronary Angiography
NCT00337337	Phase 4	UNKNOWN	Multiple Grain in Type 2 Diabetes
NCT00338104	Phase 4	COMPLETED	Conversion of Hyperglycemic Patients Being Treated With Intravenous Insulin Infusions to Lantus Insulin
NCT00339833	Phase 4	COMPLETED	The Effects of Anti-Inflammatory Treatment on Insulin Resistance in Healthy Volunteers
NCT00349362	Phase 4	COMPLETED	Testosterone for Men With Insulin Treated Type 2 Diabetes
NCT00350701	Phase 4	COMPLETED	Effect of Androgel on Type 2 Diabetic Males With Hypogonadism
NCT00354939	Phase 4	COMPLETED	Insulin Analogue With Continuous Glucose Monitoring System (CGMS) Measurement
NCT00355537	Phase 4	COMPLETED	Testosterone Replacement in Diabetes With Vascular Disease (Version 2)
NCT00359801	Phase 4	COMPLETED	Exubera Large Simple Trial To Evaluate Long-Term Pulmonary And Cardiovascular Safety
NCT00362778	Phase 4	COMPLETED	Intensive Insulin Therapy in Non-diabetic Patients With Acute Myocardial Infarction and Hyperglycaemia
NCT00365170	Phase 4	COMPLETED	Efficacy and Safety of Insulin Aspart vs. Human Insulin During Pregnancy by Women With Type 1 Diabetes
NCT00374426	Phase 4	COMPLETED	Preventing Depression Recurrence in Diabetes
NCT00385528	Phase 4	COMPLETED	Effects of a Multi-Faceted Psychiatric Intervention Targeted at the Complex Medically Ill: a Randomized Controlled Trial
NCT00390975	Phase 4	TERMINATED	Effect of Tegaserod on Gastric Emptying in Patients With Diabetic Gastroparesis
NCT00394407	Phase 4	COMPLETED	Basal/Bolus Versus Sliding Scale Insulin In Hospitalized Patients With Type 2 Diabetes
NCT00404599	Phase 4	UNKNOWN	Oxidative Stress Lowering Effect of Simvastatin and Atorvastatin.
NCT00407641	Phase 4	WITHDRAWN	Effects of Tinzaparin on Cardio-vascular Outcomes and on Blood Lipids in Diabetic Patients on Chronic Hemodialysis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ABCC8 across ~30M SureChEMBL compounds — explore on Sugi Predict.