ABCC9

Summary

ABCC9 (ATP binding cassette subfamily C member 9, HGNC:60) is a protein-coding gene on chromosome 12p12.1, encoding ATP-binding cassette sub-family C member 9 (O60706). Subunit of ATP-sensitive potassium channels (KATP).

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel-modulating subunit of the extra-pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated with cardiomyopathy dilated type 1O. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10060 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrichotic osteochondrodysplasia Cantu type (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 2,257 total — 63 pathogenic, 44 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 3 of 12 regions constrained (≈7% of expected missense variation)
• GTEx eGene: eQTL in 22 tissues, sQTL in 15 (q < 0.05)
• Phenotypes (HPO): 125
• Drug target: yes — 4 via a complex or family; 5 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 2 — Minoxidil, Pinacidil (Sulfonylurea receptor 2, Kir6.2)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_020297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:60
Approved symbol	ABCC9
Name	ATP binding cassette subfamily C member 9
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	SUR2, CMD1O
Ensembl gene	ENSG00000069431
Ensembl biotype	protein_coding
OMIM	601439
Entrez	10060

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 37 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000261200

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

ENST00000261200, ENST00000261201, ENST00000326684, ENST00000538350, ENST00000544039, ENST00000621589, ENST00000636888, ENST00000682068, ENST00000682426, ENST00000682646, ENST00000682789, ENST00000682879, ENST00000683105, ENST00000683560, ENST00000683676, ENST00000683695, ENST00000683811, ENST00000684084, ENST00000684435, ENST00000684543, ENST00000879185, ENST00000879186, ENST00000879187, ENST00000879188, ENST00000879189, ENST00000879190, ENST00000879191, ENST00000879192, ENST00000879193, ENST00000944975, ENST00000944976, ENST00000944977, ENST00000944978, ENST00001001507, ENST00001001508, ENST00001001509, ENST00001001510, ENST00001001511, ENST00001017811, ENST00001017812, ENST00001017813, ENST00001017814, ENST00001017815, ENST00001017816, ENST00001017817, ENST00001017818, ENST00001110463

RefSeq mRNA: 4 — MANE Select: NM_020297 NM_001377273, NM_001377274, NM_005691, NM_020297

CCDS: CCDS8693, CCDS8694

Canonical transcript exons

ENST00000261200 — 40 exons

Exon	Start	End
ENSE00000726469	21812049	21812157
ENSE00000726777	21844767	21844915
ENSE00000726951	21848150	21848246
ENSE00000727102	21852368	21852505
ENSE00000727996	21887826	21887934
ENSE00000728358	21910157	21910312
ENSE00000822276	21797389	21801181
ENSE00000822278	21805998	21806060
ENSE00000822280	21807346	21807479
ENSE00000822283	21809852	21809955
ENSE00000822287	21814644	21814722
ENSE00000822288	21815763	21815893
ENSE00000822290	21817187	21817307
ENSE00000822292	21818150	21818251
ENSE00000822295	21828958	21829060
ENSE00000822299	21842314	21842471
ENSE00000822300	21844483	21844552
ENSE00000822304	21845603	21845832
ENSE00000822309	21852097	21852222
ENSE00000822315	21860971	21861055
ENSE00000822317	21862953	21863054
ENSE00000822319	21872625	21872730
ENSE00000822321	21875654	21875726
ENSE00000822323	21882766	21882873
ENSE00000822326	21894032	21894174
ENSE00000822328	21906126	21906288
ENSE00000822332	21908077	21908211
ENSE00000822336	21910826	21910978
ENSE00000822338	21912872	21913066
ENSE00000822339	21915668	21915910
ENSE00000822342	21916937	21917103
ENSE00000822346	21925942	21926063
ENSE00000822347	21933782	21933923
ENSE00000994933	21864439	21864477
ENSE00000994940	21895275	21895315
ENSE00001428058	21940710	21940825
ENSE00001431495	21936533	21936694
ENSE00001606314	21859586	21859666
ENSE00001609415	21838078	21838170
ENSE00003911153	21941200	21941426

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 92.54.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1426 / max 101.0371, expressed in 498 samples.

Highest expression (Bgee): gastrocnemius, muscle of leg, hindlimb stylopod muscle, calcaneal tendon, heart left ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ABCC9 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 15 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	3.0e-53	+3.18	12:21864476:C:T
Adipose Visceral Omentum	sqtl	2.6e-26	+2.72	12:21864476:C:T
Muscle Skeletal	sqtl	3.2e-25	+0.36	12:21842021:G:C
Adipose Subcutaneous	sqtl	2.2e-22	+2.15	12:21864476:C:T
Thyroid	sqtl	4.0e-17	+2.00	12:21864476:C:T
Adrenal Gland	eqtl	1.6e-16	+0.60	12:21842621:C:A
Breast Mammary Tissue	sqtl	7.6e-14	+2.24	12:21864476:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-13	+0.36	12:21891909:C:T
Heart Atrial Appendage	sqtl	5.5e-12	+2.70	12:21864476:C:T
Brain Caudate basal ganglia	eqtl	1.0e-11	+0.31	12:21888110:GGACAGAGGGGTT:G
Nerve Tibial	sqtl	2.1e-09	+1.62	12:21864476:C:T
Artery Tibial	eqtl	9.9e-07	+0.15	12:21884168:T:C
Brain Putamen basal ganglia	eqtl	1.9e-06	+0.24	12:21871159:T:G
Pancreas	eqtl	9.2e-06	-0.31	12:21942320:G:A
Brain Cortex	eqtl	1.7e-05	+0.20	12:21891909:C:T
Lung	sqtl	1.9e-05	+1.56	12:21864476:C:T
Artery Aorta	eqtl	4.8e-05	+0.18	12:21884168:T:C
Heart Left Ventricle	sqtl	5.8e-05	+2.04	12:21864476:C:T
Brain Frontal Cortex BA9	eqtl	9.8e-05	+0.17	12:21891909:C:T
Artery Tibial	sqtl	6.7e-04	-1.47	12:21864476:C:T

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
130058	1.4307	394
130054	0.8554	337
130056	0.5101	247
130057	0.0850	39
130052	0.0712	47
130055	0.0672	34
130053	0.0635	22
130059	0.0596	24

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	92.54	gold quality
muscle of leg	UBERON:0001383	92.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.86	gold quality
calcaneal tendon	UBERON:0003701	89.45	gold quality
heart left ventricle	UBERON:0002084	88.23	gold quality
apex of heart	UBERON:0002098	87.91	gold quality
right lobe of liver	UBERON:0001114	87.87	gold quality
cardiac ventricle	UBERON:0002082	87.71	gold quality
stromal cell of endometrium	CL:0002255	87.58	gold quality
mucosa of stomach	UBERON:0001199	87.58	gold quality
muscle organ	UBERON:0001630	87.02	gold quality
buccal mucosa cell	CL:0002336	85.83	gold quality
body of uterus	UBERON:0009853	85.79	gold quality
right atrium auricular region	UBERON:0006631	85.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.67	gold quality
gall bladder	UBERON:0002110	85.50	gold quality
heart	UBERON:0000948	85.38	gold quality
smooth muscle tissue	UBERON:0001135	85.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.91	gold quality
lower esophagus	UBERON:0013473	84.88	gold quality
left uterine tube	UBERON:0001303	84.74	gold quality
omental fat pad	UBERON:0010414	83.88	gold quality
peritoneum	UBERON:0002358	83.80	gold quality
colonic epithelium	UBERON:0000397	83.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.52	gold quality
popliteal artery	UBERON:0002250	83.42	gold quality
tibial artery	UBERON:0007610	83.40	gold quality
cardiac atrium	UBERON:0002081	83.10	gold quality
islet of Langerhans	UBERON:0000006	83.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.47	gold quality
tendon	UBERON:0000043	81.92	gold quality
liver	UBERON:0002107	81.46	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.64	gold quality
biceps brachii	UBERON:0001507	80.59	gold quality
aorta	UBERON:0000947	80.39	gold quality
endocervix	UBERON:0000458	79.68	gold quality
adipose tissue	UBERON:0001013	79.03	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.94	gold quality
left ovary	UBERON:0002119	78.84	gold quality
left coronary artery	UBERON:0001626	78.75	gold quality
right coronary artery	UBERON:0001625	78.54	gold quality
deltoid	UBERON:0001476	78.53	gold quality
connective tissue	UBERON:0002384	78.45	gold quality
ectocervix	UBERON:0012249	78.30	gold quality
descending thoracic aorta	UBERON:0002345	78.16	gold quality
right lung	UBERON:0002167	78.10	gold quality
right ovary	UBERON:0002118	78.03	gold quality
adrenal tissue	UBERON:0018303	78.01	gold quality
metanephros cortex	UBERON:0010533	77.67	gold quality
right lobe of thyroid gland	UBERON:0001119	77.58	gold quality
coronary artery	UBERON:0001621	77.39	gold quality
thoracic aorta	UBERON:0001515	76.70	gold quality
heart right ventricle	UBERON:0002080	76.61	gold quality
ascending aorta	UBERON:0001496	76.55	gold quality
tibialis anterior	UBERON:0001385	76.47	gold quality
skeletal muscle tissue	UBERON:0001134	76.40	gold quality
tibial nerve	UBERON:0001323	75.87	gold quality
left lobe of thyroid gland	UBERON:0001120	75.77	gold quality
upper lobe of left lung	UBERON:0008952	75.70	gold quality
pancreas	UBERON:0001264	75.57	gold quality
thyroid gland	UBERON:0002046	75.53	gold quality
sural nerve	UBERON:0015488	75.26	gold quality
muscle tissue	UBERON:0002385	75.05	gold quality
esophagus	UBERON:0001043	75.03	gold quality
triceps brachii	UBERON:0001509	74.89	silver quality
upper lobe of lung	UBERON:0008948	74.74	gold quality
ovary	UBERON:0000992	74.51	gold quality
gluteal muscle	UBERON:0002000	73.94	silver quality
minor salivary gland	UBERON:0001830	73.78	gold quality
stomach	UBERON:0000945	73.25	gold quality
body of pancreas	UBERON:0001150	73.25	gold quality
left adrenal gland	UBERON:0001234	73.23	gold quality
adrenal gland	UBERON:0002369	72.96	gold quality
left adrenal gland cortex	UBERON:0035825	72.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	72.70	gold quality
myometrium	UBERON:0001296	72.50	gold quality
body of stomach	UBERON:0001161	72.34	gold quality
vagina	UBERON:0000996	72.12	gold quality
fundus of stomach	UBERON:0001160	71.94	gold quality
sigmoid colon	UBERON:0001159	71.79	gold quality
skin of leg	UBERON:0001511	71.55	gold quality
corpus callosum	UBERON:0002336	71.52	gold quality
lymph node	UBERON:0000029	71.40	gold quality
right uterine tube	UBERON:0001302	71.39	gold quality
amygdala	UBERON:0001876	71.14	gold quality
cingulate cortex	UBERON:0003027	70.94	gold quality
adrenal cortex	UBERON:0001235	70.88	gold quality
right adrenal gland	UBERON:0001233	70.84	gold quality
anterior cingulate cortex	UBERON:0009835	70.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.61	gold quality
ganglionic eminence	UBERON:0004023	70.46	gold quality
quadriceps femoris	UBERON:0001377	70.42	gold quality
prefrontal cortex	UBERON:0000451	70.22	gold quality
mouth mucosa	UBERON:0003729	70.09	gold quality
skin of abdomen	UBERON:0001416	69.96	gold quality
diaphragm	UBERON:0001103	69.90	gold quality
caudate nucleus	UBERON:0001873	69.89	gold quality
uterus	UBERON:0000995	69.79	gold quality
putamen	UBERON:0001874	69.63	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	179.58
E-GEOD-110499	yes	139.28
E-ANND-3	yes	15.03
E-MTAB-9067	yes	11.87
E-GEOD-81608	yes	10.79
E-GEOD-83139	yes	5.47
E-ENAD-27	yes	5.02
E-MTAB-6678	yes	5.01
E-GEOD-76312	no	177.43
E-GEOD-81547	no	7.52

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	32.8
Skeletal muscle	tissue	28.4
Liver	tissue	27.5
Postcentral gyrus	tissue	25.5
Adipose tissue	tissue	21.7
Heart muscle	tissue	19.8
Tongue	tissue	19.3
Hippocampus	tissue	18.5
Nucleus accumbens	tissue	16.1
Olfactory bulb	tissue	14.6
Smooth muscle	tissue	14.2
Locus coeruleus	tissue	13.8
Septum	tissue	13.6
Endometrium 1	tissue	13.1
Hippocampal formation	tissue	12.6
Putamen	tissue	12.4
Amygdala	tissue	12.3
Spinal cord	tissue	12.1
Hypothalamus	tissue	11.9
Periaqueductal gray	tissue	11.9
Corpus callosum	tissue	11.5
Substantia nigra	tissue	11.4
Thalamus	tissue	10.9
Ventral forebrain	tissue	10.7
Medulla oblongata	tissue	9.8
Midbrain	tissue	9.7
Basal ganglia	tissue	9.6
Cerebral cortex	tissue	9.4
Pons	tissue	9.4
Temporal cortex	tissue	9.4
Insular cortex	tissue	9.1
Prefrontal cortex	tissue	9.0
Entorhinal cortex	tissue	8.9
Gallbladder	tissue	8.8
Superior colliculi	tissue	8.5
Motor cortex	tissue	8.3
Retrosplenial cortex	tissue	7.6
Retrosplenial and cingulate cortex	tissue	7.5
Occipital cortex	tissue	7.1
Epididymis	tissue	7.0
Seminal vesicle	tissue	6.6
Somatosensory cortex	tissue	6.4
Lung	tissue	6.2
Ovary	tissue	5.9
Fallopian tube	tissue	5.8
Prostate	tissue	5.5
Kidney	tissue	5.3
Esophagus	tissue	4.6
Adrenal gland	tissue	4.5
Cerebellum	tissue	4.3
Cervix	tissue	4.1
Breast	tissue	4.1
Caudate putamen	tissue	3.9
Vagina	tissue	3.7
Urinary bladder	tissue	3.7
Spleen	tissue	3.7
Thyroid gland	tissue	3.5
Skin 1	tissue	3.2
Frontal cortex	tissue	3.1
Lymph node	tissue	2.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Periaquaductal grey, lateral (24.3), Periaquaductal grey, dorsal (24.1), Inferior parietal lobule (21.4), Area postrema (20.7), Parieto-occipital transitional area (20.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, HIF1A

Functional genomics

gnomAD constraint: pLI 7.27e-06, LOEUF 0.557, missense Z 7.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000261200 splits into 12 regions with different missense tolerance; 3 are missense-constrained (≈7% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:21,801,047–21,801,128	30 / 34.3	0.87	no
12:21,801,129–21,807,467	40 / 105.5	0.38	no
12:21,807,468–21,814,672	67 / 101.0	0.66	no
12:21,814,673–21,815,767	3 / 24.8	0.12	yes (p 1.2e-05)
12:21,815,768–21,842,326	143 / 225.6	0.63	no
12:21,842,327–21,842,471	12 / 57.2	0.21	yes (p 2.2e-09)
12:21,844,483–21,845,713	74 / 132.7	0.56	no
12:21,845,714–21,852,445	131 / 170.2	0.77	no
12:21,852,446–21,861,031	31 / 78.8	0.39	no
12:21,861,032–21,906,200	258 / 325.6	0.79	no
12:21,906,201–21,908,117	8 / 47.5	0.17	yes (p 9.7e-09)
12:21,908,118–21,936,674	305 / 573.0	0.53	no

Literature-anchored findings (GeneRIF, showing 40)

• Assembly limits the pharmacological complexity of ATP-sensitive potassium channels (PMID:11825905)
• down-regulation of this channel may facilitate myometrial function during late pregnancy (PMID:12356945)
• In corporal smooth muscle is composed of Kir6.1-Kir6.2 construct expressed with SUR2B.K(ATP) channel in corporal smooth muscle cells is composed of heteromultimers of Kir6.1 and Kir6.2 with the ratio of 3 : 1 or 4 : 0 and SUR2B. (PMID:12934053)
• role of mutation in human dilated cardiomyopathy and effect on KATP channel gating (PMID:15034580)
• Syn-1A binds both NBFs of SUR1 and SUR2A but appears to exhibit distinct interactions with NBF2 of these SUR proteins in modulating the KATP channels in islet beta cells and cardiac myocytes (PMID:15339904)
• Syn-1A binds both NBFs of SUR1 and SUR2A but appears to exhibit distinct interactions with NBF2 of these SUR proteins in modulating the KATP channels in islet beta cells and cardiac myocytes (PMID:16267564)
• newly discovered 734Ile allele in ABCC9 might influence susceptibility to precocious myocardial infarct in our population (PMID:16563363)
• Syntaxin-1A actions on sulfonylurea receptor 2A blocks acidic pH-induced cardiac K(ATP) channel activation (PMID:16672225)
• Results describe a new function of the Kir6.1-SUR2A complex, namely the regulation of paracellular permeability through tight junctions. (PMID:16820413)
• review the structure and function of ABC proteins and discuss SUR, its regulation of the K(ATP) channel, and its role in cardiovascular disease. (PMID:18239147)
• caveolin-dependent internalization is involved in PKC-epsilon-mediated inhibition of vascular K(ATP) channels (Kir6.1 and SUR2B) by phorbol 12-myristate 13-acetate or angiotensin II (PMID:18663158)
• Kir6.1/SUR2B is the major functional K(ATP) channel complex in the pig MMA and MCA, and mRNA expression studies suggest that the human MMA shares this K(ATP) channel subunit profile (PMID:18996111)
• caveolin-3 negatively regulates Kir6.2/SUR2A channel function. (PMID:19481058)
• sequence variants in ABCC9 is unlikely to contribute to variation in postural change in systolic blood pressure (PMID:19952277)
• These findings suggest that abnormal localization of the SUR2A K(+) channel protein leads to reduced K(ATP) channel activity in familial hypokalemic periodic paralysis. (PMID:19962959)
• mammalian oocytes express K(ATP) channels. Real-time PCR revealed that mRNA for Kir6.1, Kir6.2, SUR2A and SUR2B, were present in human oocytes of different stages. (PMID:20847183)
• This study showed that variants in the SUR2 gene (ABCC9) associate with epidemiological variation in human sleep duration, which is also influenced by inter-individual differences in seasonal adaptation and chronotype. (PMID:22105623)
• Cantu syndrome is caused by mutations in ABCC9 (PMID:22608503)
• Electrophysiological experiments show that mutations in ABCC9, associated with Cantu syndrome, reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. (PMID:22610116)
• two different de novo missense mutations in the two patients with coarse facial features and hypertrichosis (PMID:23307537)
• A mutation (V734I) in ABCC9 increases susceptibility to coronary spasm and acute myocardial infarction. (PMID:23739550)
• ABCC9 is a susceptibility gene for early repolarization syndrome and Brugada syndrome. (PMID:24439875)
• Results show that a polymorphism in ABCC9 is associated with aging pathology, and exposure to sulfonylurea drugs is associated with increased risk for aging pathology among individuals who died age 85 and older (PMID:24770881)
• This study confirmed that specific ABCC9 single-nucleotide polymorphisms is associated with HS-Aging pathology in the Alzheimer disease. (PMID:25470345)
• We describe novel ABCC9 variants in human brain, corresponding to altered 3’UTR length, which could lead to targeting by miR-30c (PMID:26115089)
• single amino acid difference can account for the markedly different diazoxide sensitivities between channels containing either the SUR1 or SUR2A subunit isoforms. (PMID:26181369)
• ABCC9 polymorphism associated with Brain disorders: sleep problems. depression and HS-Aging. (PMID:26226329)
• Analysis of three Cantu syndrome-associated gain of function mutations indicates that all lead to overactive K(ATP) channels, but at least two mechanisms underlie the observed gain of function: decreased ATP inhibition and enhanced MgADP activation. (PMID:26621776)
• The patient reported here gives further evidence that these syndromes are an expression of the ABCC9-related disorders, ranging from hypertrichosis and acromegaloid facies to the severe end of Cantu syndrome. (PMID:26871653)
• ABCC9 gene has been associated with Dilated Cardiomyopathy. 3 pathogenic variants have been associated with DCM: 1 missense -CM1410876-, 1 nonsense -CM040975-, and 1 small indel -CX041212. (PMID:27736720)
• Significant gene-based association between the ABCC9 gene and hippocampal sclerosis-aging appeared to be driven by a region in which a significant haplotype-based association. (PMID:28131462)
• ABCC9-related Intellectual disability Myopathy Syndrome is a K(ATP) channelopathy with loss-of-function mutations in ABCC9. (PMID:31575858)
• Three-dimensional facial morphology in Cantu syndrome. (PMID:32100467)
• Novel variants of ABCC9 in Japanese children with Cantu syndrome. (PMID:32198910)
• Cantu syndrome versus Zimmermann-Laband syndrome: Report of nine individuals with ABCC9 variants. (PMID:32622958)
• Novel cholesterol-dependent regulation of cardiac KATP subunit expression revealed using histone deacetylase inhibitors. (PMID:33356020)
• Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development. (PMID:33432820)
• The expression of ATP-sensitive potassium channels in human umbilical arteries with severe pre-eclampsia. (PMID:33846486)
• Consequences of SUR2[A478V] Mutation in Skeletal Muscle of Murine Model of Cantu Syndrome. (PMID:34359961)
• Vascular KATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides. (PMID:34711681)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcc9	ENSDARG00000015985
mus_musculus	Abcc9	ENSMUSG00000030249
rattus_norvegicus	Abcc9	ENSRNOG00000036960
drosophila_melanogaster	l(2)03659	FBGN0010549
drosophila_melanogaster	CG7627	FBGN0032026
drosophila_melanogaster	MRP	FBGN0032456
drosophila_melanogaster	CG9270	FBGN0032908
drosophila_melanogaster	CG10505	FBGN0034612
drosophila_melanogaster	Mrp5	FBGN0038740
drosophila_melanogaster	rdog	FBGN0039644
drosophila_melanogaster	CG11898	FBGN0039645
drosophila_melanogaster	CG31792	FBGN0051792
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477

Paralogs (11): CFTR (ENSG00000001626), ABCC8 (ENSG00000006071), ABCC2 (ENSG00000023839), 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:1352630) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 46 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged heart	3
dilated heart left ventricle	2
increased heart weight	2
abnormal channel response	2
abnormal heart echocardiography feature	2
increased monocyte cell number	1
abnormal blood vessel physiology	1
abnormal myocardial fiber morphology	1
abnormal response to cardiac infarction	1
hypotension	1
cardiac hypertrophy	1
premature death	1
increased systemic arterial blood pressure	1
decreased myocardial infarct size	1
abnormal impulse conducting system conduction	1
increased cardiac output	1
increased muscle fatigability	1
oxidative stress	1
abnormal sarcolemma morphology	1
abnormal myocardial fiber physiology	1
dilated heart	1
decreased lymphocyte cell number	1
hypoxia	1
decreased cardiac muscle contractility	1
decreased oxygen consumption	1

+21 more (showing top 25).

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
Cryptococcus neoformans H99	J9VQH1	42.5%	Diamond
Mycosarcoma maydis	A0A0D1CZ63	41.8%	Diamond
Aspergillus versicolor	P9WEL8	41.0%	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
KCNJ8-AS1	ncRNA	105369689
GYS2	protein-coding	2998
KCNJ8	protein-coding	3764
LDHB	protein-coding	3945
CMAS	protein-coding	55907
ST8SIA1	protein-coding	6489

Protein

Protein identifiers

ATP-binding cassette sub-family C member 9 — O60706 (reviewed: O60706)

Alternative names: Sulfonylurea receptor 2

All UniProt accessions (10): A0A804HHX2, A0A804HIU2, A0A804HK56, A0A804HKB7, A0A804HL22, A0A804HL58, O60706, G3V1N6, H0YFV4, Q8N4N7

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation. Can form a sulfonylurea-sensitive but ATP-insensitive potassium channel with KCNJ8.

Subunit / interactions. Interacts with KCNJ11. Interacts with KCNJ8.

Subcellular location. Membrane.

Disease relevance. Cardiomyopathy, dilated, 1O (CMD1O) [MIM:608569] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Atrial fibrillation, familial, 12 (ATFB12) [MIM:614050] A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. The disease is caused by variants affecting the gene represented in this entry. Hypertrichotic osteochondrodysplasia (HTOCD) [MIM:239850] A rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability. The disease is caused by variants affecting the gene represented in this entry. Intellectual disability and myopathy syndrome (IDMYS) [MIM:619719] An autosomal recessive disorder characterized by global developmental delay, mildly impaired intellectual development, hypotonia, muscle weakness and fatigue, and white matter abnormalities on brain imaging. Variable additional features may include sensorineural hearing loss, dysmorphic facies, and progressive heart disease. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May contribute to the regulation of sleep duration. An intronic variant of this gene may account for about 5% of the variation of sleep duration between individuals. Sleep duration is influenced both by environmental and genetic factors, with an estimated heritability of about 40%. Numerous genes are expected to contribute to the regulation of sleep duration.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O60706-1	SUR2A	yes
O60706-2	SUR2B

RefSeq proteins (4): NP_001364202, NP_001364203, NP_005682, NP_064693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000388	ABCC8/9	Family
IPR001475	ABCC9	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
IPR047080	ABCC9_ATP-bd_dom1	Domain
IPR050173	ABC_transporter_C-like	Family

Pfam: PF00005, PF00664

UniProt features (66 total): sequence variant 17, topological domain 16, transmembrane region 15, glycosylation site 5, domain 4, sequence conflict 3, binding site 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60706-F1	81.72	0.35

Human Protein Atlas

Protein class: Metabolic proteins, Transporters, Primary Active Transporters, Predicted membrane proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; plasma membrane

Antibody reliability (HPA): IH uncertain · 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 (2)

Position	Role
705–712	ATP
1346–1353	ATP

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	9, 326, 330, 333, 334

Function

Pathways and Gene Ontology

Reactome pathways

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

13 pathways:

ID	Pathway	Evidence
R-HSA-5678420	Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome ⚕	curated
R-HSA-382556	ABC-family protein mediated transport	curated
R-HSA-1296025	ATP sensitive Potassium channels	curated
R-HSA-5578775	Ion homeostasis	curated
R-HSA-5619084	ABC transporter disorders ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-5576891	Cardiac conduction	—
R-HSA-1296065	Inwardly rectifying K+ channels	—
R-HSA-397014	Muscle contraction	—
R-HSA-112316	Neuronal System	—
R-HSA-1296071	Potassium Channels	—
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 554 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_LIPID_MODIFICATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, GOBP_RESPONSE_TO_POTASSIUM_ION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (9): response to ATP (GO:0033198), defense response to virus (GO:0051607), transmembrane transport (GO:0055085), cardiac conduction (GO:0061337), potassium ion transmembrane transport (GO:0071805), monoatomic cation transmembrane transport (GO:0098655), transport across blood-brain barrier (GO:0150104), potassium ion import across plasma membrane (GO:1990573), potassium ion transport (GO:0006813)

GO Molecular Function (15): potassium channel activity (GO:0005267), ATP binding (GO:0005524), sulfonylurea receptor activity (GO:0008281), potassium channel regulator activity (GO:0015459), ATP hydrolysis activity (GO:0016887), ATPase-coupled monoatomic cation transmembrane transporter activity (GO:0019829), ATPase-coupled transmembrane transporter activity (GO:0042626), transmembrane transporter binding (GO:0044325), protein-containing complex binding (GO:0044877), potassium channel activator activity (GO:0099104), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), inward rectifier potassium channel activity (GO:0005242), ATP-activated inward rectifier potassium channel activity (GO:0015272), transmembrane transporter activity (GO:0022857)

GO Cellular Component (9): mitochondrion (GO:0005739), plasma membrane (GO:0005886), inward rectifying potassium channel (GO:0008282), sarcomere (GO:0030017), potassium ion-transporting ATPase complex (GO:0031004), sarcolemma (GO:0042383), cytoplasm (GO:0005737), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Inwardly rectifying K+ channels	1
Transport of small molecules	1
Cardiac conduction	1
ABC transporter disorders	1
Potassium Channels	1
Neuronal System	1
Muscle contraction	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

54 GO namespaces:

Category	Terms
cellular anatomical structure	3
potassium channel activity	2
ATP-dependent activity	2
ATPase-coupled transmembrane transporter activity	2
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
defense response	1
response to virus	1
transport	1
cellular process	1
regulation of heart contraction	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
vascular transport	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
metal ion transport	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transmembrane signaling receptor activity	1
ion channel regulator activity	1
ribonucleoside triphosphate phosphatase activity	1
monoatomic cation transmembrane transporter activity	1
active monoatomic ion transmembrane transporter activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
protein binding	1
binding	1
potassium channel regulator activity	1
channel activator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
inward rectifier potassium channel activity	1
transporter activity	1
transmembrane transport	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
myofibril	1
cation-transporting ATPase complex	1
plasma membrane	1
intracellular anatomical structure	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 33 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
cardiac conduction	BP	mutant phenotype
defense response to virus	BP	mutant phenotype
potassium ion transmembrane transport	BP	mutant phenotype
response to ATP	BP	mutant phenotype
inward rectifying potassium channel	CC	direct assay
ATPase-coupled transmembrane transporter activity	MF	direct assay
transmembrane transporter binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,170 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC9	KCNJ8	Q15842	850
ABCC9	KCNJ11	Q14654	825
ABCC9	RBM20	Q5T481	807
ABCC9	SCN5A	Q14524	741
ABCC9	CSRP3	P50461	718
ABCC9	MYBPC3	Q14896	717
ABCC9	EYA4	O95677	713
ABCC9	NEXN	Q0ZGT2	707
ABCC9	DSG2	Q14126	707
ABCC9	TMPO	P08918	703
ABCC9	LDB3	O75112	698
ABCC9	TCAP	O15273	683
ABCC9	SGCD	Q92629	679
ABCC9	ACTN2	P35609	661
ABCC9	ACTC1	P04270	657

IntAct

Human interaction partners of ABCC9 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
HSPB2	physical association	0.370	1
ABCC8	association	0.350	1
KCNJ11	proximity	0.270	1

BioGRID (7 interactions; top human partners by supporting records): ABCC8 (Affinity Capture-MS), EEF1G (Two-hybrid), ESF1 (Cross-Linking-MS (XL-MS)), HSPB2 (Two-hybrid), LDHA (Affinity Capture-Western)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
ABCC9	“form complex”	“KATP channel”	binding

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
★ ABCC9-KCNJ11-LDHA (muscle form) complex	3	ABCC9, KCNJ11, LDHA
★ ABCC9-KCNJ11 complex	2	ABCC9, KCNJ11

Disease & clinical

Genetic variants

Variant evidence for ABCC9: 2,257 ClinVar records (107 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,257 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	44
Uncertain significance	971
Likely benign	859
Benign	113

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 107 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
31947	NM_020297.4(ABCC9):c.3461G>A (p.Arg1154Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
35533	NM_020297.4(ABCC9):c.3347G>A (p.Arg1116His)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1486684	NM_020297.4(ABCC9):c.1057_1073dup (p.Phe359_Leu360insTerPhe)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
265666	NM_020297.4(ABCC9):c.3460C>G (p.Arg1154Gly)	Pathogenic	criteria provided, single submitter	1
666063	NM_020297.4(ABCC9):c.4202del (p.Gly1401fs)	Pathogenic	criteria provided, single submitter	1
841170	NM_020297.4(ABCC9):c.1686del (p.Ser562fs)	Pathogenic	criteria provided, single submitter	1
963311	NM_020297.4(ABCC9):c.3673dup (p.Tyr1225fs)	Pathogenic	criteria provided, single submitter	1
1000443	NM_020297.4(ABCC9):c.2721T>G (p.Tyr907Ter)	Pathogenic	criteria provided, single submitter	1
1022992	NM_020297.4(ABCC9):c.2371C>T (p.Gln791Ter)	Pathogenic	criteria provided, single submitter	1
1026876	NM_020297.4(ABCC9):c.2422_2423del (p.Arg808fs)	Pathogenic	criteria provided, single submitter	1
1035485	NM_020297.4(ABCC9):c.438del (p.Thr147fs)	Pathogenic	criteria provided, single submitter	1
1044828	NM_020297.4(ABCC9):c.2826T>G (p.Tyr942Ter)	Pathogenic	criteria provided, single submitter	1
1057737	NM_020297.4(ABCC9):c.2529_2530del (p.Ile844fs)	Pathogenic	criteria provided, single submitter	1
1395006	NM_020297.4(ABCC9):c.1022_1032dup (p.Lys345fs)	Pathogenic	criteria provided, single submitter	1
1402291	NM_020297.4(ABCC9):c.3269del (p.Gly1090fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ABCC9’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; 43 predictions of 3,350):

Position(s)	Effect	Δscore	Sites
12:21801084	donor_gain	1.0000
12:21805996–21805997	donor_loss	1.0000	5
12:21806061–21806062	acceptor_loss	1.0000	6
12:21815761–21815762	donor_loss	1.0000	4
12:21829061–21829062	acceptor_loss	1.0000	5
12:21838171–21838172	acceptor_loss	1.0000	6
12:21852096	donor_loss	1.0000	2
12:21875652–21875653	donor_loss	1.0000	5
12:21875727–21875728	acceptor_loss	1.0000	6
12:21882882–21882885	acceptor_gain	1.0000	3

AlphaMissense

5,232 missense substitutions predicted likely pathogenic (of 10,169 scored), across 1,174 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
M722	9	0.974	0.999
M425	9	0.899	0.994
M914	9	0.851	0.972
M437	9	0.845	0.997
M255	9	0.833	0.984
D836	8	0.999	1.000
D843	8	0.999	1.000
D1473	8	0.999	1.000
D1480	8	0.997	0.999
D793	8	0.996	0.999
D837	8	0.996	0.999
D308	8	0.995	0.999
D207	8	0.994	0.998
H871	8	0.993	0.999
D1104	8	0.993	0.998
D1012	8	0.992	0.998
S813	8	0.990	0.999
F578	8	0.989	0.998
F1495	8	0.987	0.998
D210	8	0.986	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000168
Colon Adenocarcinoma (TCGA)	unfavorable	0.000723
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000988

Disease associations

OMIM: gene MIM:601439 | disease phenotypes: MIM:608569, MIM:239850, MIM:619719, MIM:607411, MIM:610253, MIM:194200

GenCC curated gene-disease

7 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypertrichotic osteochondrodysplasia Cantu type	Definitive	Autosomal dominant	5
dilated cardiomyopathy 1O	Strong	Autosomal dominant	4
intellectual disability and myopathy syndrome	Strong	Autosomal recessive	4
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
Brugada syndrome	Limited	Autosomal dominant	2
atrial fibrillation, familial, 12	Limited	Unknown
familial dilated cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

3 validity classifications:

Disease	Classification	Inheritance
Brugada syndrome	Disputed	AD
hypertrichotic osteochondrodysplasia Cantu type	Definitive	AD
dilated cardiomyopathy 1O	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
DDG2P	green
Dilated Cardiomyopathy and conduction defects	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Paediatric or syndromic cardiomyopathy	green
Skeletal dysplasia	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (11): dilated cardiomyopathy 1O (MONDO:0012062), hypertrichotic osteochondrodysplasia Cantu type (MONDO:0009406), intellectual disability and myopathy syndrome (MONDO:0859224), patent ductus arteriosus (MONDO:0011827), Kleefstra syndrome 1 (MONDO:0027407), cardiomyopathy (MONDO:0004994), Wolff-Parkinson-White syndrome (MONDO:0008685), Brugada syndrome (MONDO:0015263), atrial fibrillation, familial, 12 (MONDO:0013545), (MONDO:0015470), familial dilated cardiomyopathy (MONDO:0016333)

Orphanet (7): Familial isolated dilated cardiomyopathy (Orphanet:154), Cantú syndrome (Orphanet:1517), Kleefstra syndrome (Orphanet:261494), Rare cardiomyopathy (Orphanet:167848), Familial patent arterial duct (Orphanet:466729), NON RARE IN EUROPE: Patent arterial duct (Orphanet:706), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

showing 60 of 125 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000215	Thick upper lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000336	Prominent supraorbital ridges
HP:0000343	Long philtrum
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000527	Long eyelashes
HP:0000565	Esotropia
HP:0000574	Thick eyebrow
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000689	Dental malocclusion
HP:0000739	Anxiety
HP:0000774	Narrow chest
HP:0000885	Broad ribs
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0000944	Abnormal metaphysis morphology
HP:0000957	Cafe-au-lait spot
HP:0000965	Cutis marmorata
HP:0000969	Edema
HP:0001004	Lymphedema
HP:0001047	Atopic dermatitis
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001279	Syncope
HP:0001374	Congenital hip dislocation
HP:0001377	Limited elbow extension
HP:0001520	Large for gestational age
HP:0001537	Umbilical hernia
HP:0001566	Widely-spaced maxillary central incisors
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001644	Dilated cardiomyopathy
HP:0001647	Bicuspid aortic valve
HP:0001649	Tachycardia
HP:0001654	Abnormal heart valve morphology
HP:0001658	Myocardial infarction
HP:0001663	Ventricular fibrillation
HP:0001695	Cardiac arrest
HP:0001698	Pericardial effusion
HP:0001727	Thromboembolic stroke
HP:0001771	Achilles tendon contracture
HP:0001869	Deep plantar creases
HP:0001907	Thromboembolism
HP:0001962	Palpitations

GWAS associations

11 associations:

Study	Trait	p-value
GCST006629_39	Pulse pressure	7e-20
GCST90000025_528	Appendicular lean mass	8e-15
GCST007269_198	Pulse pressure	2e-14
GCST90000027_44	Appendicular lean mass	2e-10
GCST002430_1	Hippocampal sclerosis of aging	1e-9
GCST008363_121	Offspring birth weight	3e-8
GCST001356_5	Gout	1e-7
GCST005146_58	Birth weight	1e-7
GCST90000026_13	Appendicular lean mass	4e-6
GCST001762_947	Obesity-related traits	5e-6
GCST004862_24	Itch intensity from mosquito bite adjusted by bite size	5e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004344	birth weight
EFO:0005763	pulse pressure measurement
EFO:0005939	parental genotype effect measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors

8 disease descriptors:

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D009202	Cardiomyopathies	C14.280.238
D004374	Ductus Arteriosus, Patent	C14.240.400.340; C14.280.400.340; C16.131.240.400.340
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C535572	Cantu syndrome *(supp.)*
C563906	Cardiomyopathy, Dilated, 1o *(supp.)*
C563043	Kleefstra Syndrome *(supp.)*
C536231	familial dilated cardiomyopathy *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1971 (SINGLE PROTEIN), CHEMBL2095152 (PROTEIN COMPLEX GROUP), CHEMBL2095198 (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 ABCC9 — the drug acts on the assembly or class, not necessarily on this subunit alone.

4 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
MINOXIDIL	Sulfonylurea receptor 2, Kir6.2	2	4
PINACIDIL	Sulfonylurea receptor 2, Kir6.2	2	4
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: 73,038 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL472	GLYBURIDE	4	53,640
CHEMBL1159	PINACIDIL ANHYDROUS	4	6,365
CHEMBL631	PROPAFENONE	4	12,817
CHEMBL12531	CLAMIKALANT	2	80
CHEMBL49035	CROMAKALIM	2	136

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs704212	Metabolism/PK	3	montelukast	Asthma

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs704212	ABCC9	3	2.00	1	montelukast

PharmGKB variant annotations

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

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs704212	montelukast	Metabolism/PK	Allele T is associated with decreased concentrations of montelukast in healthy individuals as compared to allele C.	PMID:28940478
rs704212		Other	Allele T is associated with increased expression of ABCC9 as compared to allele C.	PMID:28940478
rs11046209	dexmedetomidine	Efficacy	Genotype AA is associated with increased severity of sedation when treated with dexmedetomidine in people with surgery as compared to genotypes AT + TT.	PMID:37693312

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
compound 13b [PMID: 19101153]	Positive	6.17	pEC50

Binding affinities (BindingDB)

149 measured of 169 human assays (172 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL217511	EC50	0.676 nM
CHEMBL426334	EC50	0.912 nM
CHEMBL218564	EC50	1 nM
CHEMBL214561	EC50	1.2 nM
CHEMBL413532	EC50	1.8 nM
CHEMBL217810	EC50	2.8 nM
CHEMBL217847	EC50	6 nM
CHEMBL386363	EC50	9.8 nM
CHEMBL265269	EC50	14 nM
CHEMBL216766	EC50	17 nM
CHEMBL216284	EC50	18 nM
CHEMBL216546	EC50	22.9 nM
CHEMBL386582	EC50	26.9 nM
CHEMBL261996	EC50	27 nM
CHEMBL214841	EC50	27.5 nM
CHEMBL386323	EC50	30 nM
CHEMBL412838	EC50	56 nM
CHEMBL3138600	EC50	56 nM
1N-cyanoimino(tert-pentylamino)methyl-3-azido-4-iodoaniline	KI	57 nM
(-)-3-chlorophenyl (3S,4R)-6-cyano-3-hydroxy-2,2-dimethylchroman-4-ylcarbamate	EC50	70 nM
CHEMBL424726	EC50	72 nM
1N-cyanoimino(tert-pentylamino)methyl-4-iodoaniline	KI	74 nM
N’’-cyano-N-(4-cyanophenyl)-N’-(1,2,2-trimethylpropyl)guanidine	KI	99 nM
WAY-133537	EC50	102 nM
CHEMBL385908	EC50	102 nM
CHEMBL384078	EC50	102 nM
(+/-)-3-chlorophenyl 6-cyano-3-hydroxy-2,2-dimethylchroman-4-ylcarbamate	EC50	120 nM
CHEMBL217696	EC50	120 nM
CHEMBL320983	EC50	126 nM
CHEMBL214566	EC50	129 nM
CHEMBL384576	EC50	129 nM
CHEMBL424909	EC50	129 nM
CHEMBL3138574	EC50	135 nM
CHEMBL384564	EC50	144 nM
CHEMBL215124	EC50	151 nM
CHEMBL215027	EC50	155 nM
CHEMBL3138607	EC50	158 nM
4-cyanoimino(tert-pentylamino)methylaminobenzonitrile	KI	160 nM
CHEMBL386119	EC50	165 nM
CHEMBL216256	EC50	169 nM
CHEMBL215375	EC50	169 nM
CHEMBL217033	EC50	218 nM
CHEMBL3138599	EC50	224 nM
CHEMBL408199	EC50	251 nM
(3S,4R)-3-hydroxy-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydro-2H-chromene-6-carbonitrile	EC50	257 nM
CHEMBL215996	EC50	257 nM
CHEMBL426874	EC50	281 nM
CHEMBL386126	EC50	295 nM
CHEMBL386136	EC50	309 nM
(+/-)-3-chlorophenyl 6-cyano-3-hydroxy-2,2-dimethylchroman-4-yl carbonate	EC50	310 nM

ChEMBL bioactivities

536 potent at pChembl≥5 of 582 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.27	EC50	0.537	nM	CHEMBL321455
9.17	EC50	0.6761	nM	CHEMBL217511
9.04	EC50	0.912	nM	CHEMBL426334
9.00	EC50	1	nM	CHEMBL218564
8.93	EC50	1.175	nM	CHEMBL214561
8.74	EC50	1.82	nM	CHEMBL413532
8.56	EC50	2.754	nM	CHEMBL217810
8.43	EC50	3.715	nM	CHEMBL218564
8.41	EC50	3.89	nM	CHEMBL384564
8.30	EC50	5.012	nM	CHEMBL3138573
8.30	EC50	5.012	nM	CHEMBL2111694
8.29	EC50	5.129	nM	CHEMBL218564
8.26	EC50	5.495	nM	CHEMBL426334
8.22	EC50	6.026	nM	CHEMBL217847
8.20	EC50	6.31	nM	CHEMBL323159
8.06	EC50	8.71	nM	CHEMBL3392139
8.05	EC50	8.913	nM	CHEMBL50760
8.01	EC50	9.772	nM	CHEMBL386363
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	CHEMBL386119
7.85	EC50	14.13	nM	CHEMBL108251
7.84	EC50	14.45	nM	CHEMBL265269
7.77	EC50	16.98	nM	CHEMBL216766
7.74	EC50	18.2	nM	CHEMBL216284
7.72	EC50	19.05	nM	CHEMBL215375
7.70	EC50	19.95	nM	CHEMBL386119
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	CHEMBL216546
7.64	EC50	22.91	nM	CHEMBL3138607
7.63	EC50	23.44	nM	CHEMBL110399
7.62	EC50	23.99	nM	CHEMBL386582
7.59	EC50	25.7	nM	CHEMBL3138549
7.59	EC50	25.7	nM	CHEMBL2112487
7.57	EC50	26.92	nM	CHEMBL386582
7.57	EC50	26.92	nM	CHEMBL261996
7.57	EC50	26.92	nM	CHEMBL426160
7.57	Ki	27	nM	CHEMBL11458
7.57	EC50	26.92	nM	CHEMBL320983
7.56	EC50	27.54	nM	CHEMBL384576
7.56	EC50	27.54	nM	CHEMBL214841
7.56	EC50	27.54	nM	CHEMBL320983
7.56	EC50	27.54	nM	CHEMBL108586
7.55	EC50	28.18	nM	CHEMBL3138545
7.54	EC50	28.84	nM	CHEMBL214841
7.53	EC50	29.51	nM	CHEMBL386323

PubChem BioAssay actives

547 with measured affinity, of 1101 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
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
8-(3-bromo-4-fluorophenyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	ec50	0.0007	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-methyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0009	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-propyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0010	uM
(4R,8S)-8-(3-bromo-4-fluorophenyl)-4-ethyl-12-oxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0012	uM
(8R,13R)-8-(3-bromo-4-fluorophenyl)-13-methyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0018	uM
(4S,8S)-8-(3-bromo-4-fluorophenyl)-4,5-dimethyl-12-oxa-2,5-diazatricyclo[7.4.0.03,7]tridec-3(7)-ene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0028	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0039	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
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-5,11-dioxa-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0060	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
(4R,8R)-8-(3-bromo-4-fluorophenyl)-4-(methoxymethyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0098	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
(4S,9R)-9-(3-bromo-4-fluorophenyl)-4-ethyl-5,13-dioxa-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0141	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-11,11-dimethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0144	uM
9-(3-bromo-4-fluorophenyl)-6,6-dimethyl-5,13-dioxa-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0170	uM
(8R,13R)-8-(3-bromo-4-fluorophenyl)-13-ethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0182	uM
(4R,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	ec50	0.0191	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	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	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
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-(methoxymethyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0229	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
8-(3-bromo-4-fluorophenyl)-11,11-dimethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0240	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
8-(3-bromo-4-fluorophenyl)-4,4-dimethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0269	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
(4R,8R)-8-(4-fluoro-3-iodophenyl)-4-propyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR 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
(4R,8R)-8-(3-bromo-4-fluorophenyl)-4-propyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0275	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-(2-methylpropyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR 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
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-butyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0295	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	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	3
Acetaminophen	increases expression, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
diallyl trisulfide	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Docetaxel	decreases response to substance, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Niclosamide	decreases expression	1
Progesterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1

ChEMBL screening assays

61 unique, capped per target: 46 functional, 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1006149	Binding	Channel opening activity at SUR2B/Kir6.2 potassium ATP channel in human TE671 cells assessed as isometric force by FLIPR	Discovery and structure-activity relationships of a novel series of benzopyran-based K(ATP) openers for urge urinary incontinence. — *Bioorg Med Chem*
CHEMBL678531	Functional	Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	Structure-Activity studies for a novel series of tricyclic dihydropyrimidines as K(ATP) channel openers (KCOs). — *Bioorg Med Chem Lett*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JT	PrecisION hKir6.2/SUR2A (KATP)-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 352 trials:

NCT	Phase	Status	Title
NCT00702117	Phase 4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT01798992	Phase 4	COMPLETED	Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart
NCT00348530	Phase 4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	Phase 4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	Phase 4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	Phase 4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	Phase 4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	Phase 4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	Phase 4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	Phase 4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	Phase 4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	Phase 4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	Phase 4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	Phase 4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	Phase 4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	Phase 4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	Phase 4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	Phase 4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	Phase 4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05371496	Phase 4	COMPLETED	Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
NCT05718128	Phase 4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	Phase 4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00701077	Phase 3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	Phase 3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT00170183	Phase 3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	Phase 3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	Phase 3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	Phase 3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	Phase 3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	Phase 3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	Phase 3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	Phase 3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	Phase 3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	Phase 3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	Phase 3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	Phase 3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	Phase 3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	Phase 3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	Phase 3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	Phase 3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	Phase 3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	Phase 3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT02933437	Phase 2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT07146880	Phase 2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT02033278	Phase 2	TERMINATED	Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
NCT00185250	Phase 2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	Phase 2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	Phase 2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy
NCT01102140	Phase 2	TERMINATED	The Impact of Pomegranate Extract on Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study
NCT01442129	Phase 2	COMPLETED	The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in Patients Undergoing LVAD Implantation
NCT01636570	Phase 2	COMPLETED	Vitamin D3 Supplementation for Heart Failure Patients
NCT01643330	Phase 2	COMPLETED	A Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure
NCT02016365	Phase 2	COMPLETED	Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
NCT02362646	Phase 2	COMPLETED	Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
NCT02485938	Phase 2	COMPLETED	HOPE-Duchenne (Halt cardiomyOPathy progrEssion in Duchenne)
NCT02681913	Phase 2	UNKNOWN	Adenosine as an Adjunct to Blood Cardioplegia
NCT04304560	Phase 2	UNKNOWN	Value of SGLT2 Inhibitor (Dapagliflozin) as an Added Therapy in Diabetic Patients With Heart Failure With Reduced Ejection Fraction; Randomized Controlled Clinical Trial
NCT06080074	Phase 2	RECRUITING	Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System
NCT00696410	Phase 1	COMPLETED	The Impact of Zinc Supplementation on Left Ventricular Function in Nonischemic Cardiomyopathy
NCT02077010	Phase 1	COMPLETED	Nebulized Inhaled Milrinone in a Hospitalized Advanced Heart Failure Population

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ABCC9 across ~30M SureChEMBL compounds — explore on Sugi Predict.