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) — +7 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 2,182 total — 65 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 125
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• 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: 33 — 24 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

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

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.

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

288 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, HIF1A

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)

Protein

Protein identifiers

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

Alternative names: Sulfonylurea receptor 2

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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 705–712; 1346–1353

Glycosylation sites (5): 9, 326, 330, 333, 334

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

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

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 (54): MAPK cascade (GO:0000165), action potential (GO:0001508), response to hypoxia (GO:0001666), heart morphogenesis (GO:0003007), regulation of transcription by RNA polymerase II (GO:0006357), mitochondrion organization (GO:0007005), skeletal muscle tissue development (GO:0007519), gene expression (GO:0010467), response to activity (GO:0014823), fatty acid oxidation (GO:0019395), response to ATP (GO:0033198), cellular response to potassium ion (GO:0035865), vasodilation (GO:0042311), response to hydrogen peroxide (GO:0042542), negative regulation of apoptotic process (GO:0043066), response to estrogen (GO:0043627), cellular respiration (GO:0045333), negative regulation of blood pressure (GO:0045776), ATP metabolic process (GO:0046034), fibroblast proliferation (GO:0048144), defense response to virus (GO:0051607), transmembrane transport (GO:0055085), coronary vasculature development (GO:0060976), cardiac conduction (GO:0061337), cellular response to chemical stress (GO:0062197), cellular response to calcium ion (GO:0071277), cellular response to ATP (GO:0071318), cellular response to xenobiotic stimulus (GO:0071466), potassium ion transmembrane transport (GO:0071805), oxygen metabolic process (GO:0072592), cardiac muscle cell contraction (GO:0086003), monoatomic cation transmembrane transport (GO:0098655), obsolete inorganic cation transmembrane transport (GO:0098662), transport across blood-brain barrier (GO:0150104), regulation of potassium ion transmembrane transport (GO:1901379), response to peptide (GO:1901652), reactive oxygen species biosynthetic process (GO:1903409), response to hydrogen sulfide (GO:1904880), potassium ion import across plasma membrane (GO:1990573), blood vessel development (GO:0001568)

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), obsolete ATPase-coupled inorganic anion transmembrane transporter activity (GO:0043225), 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), 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

Rollup of top-9 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
potassium channel activity	2
ATP-dependent activity	2
ATPase-coupled transmembrane transporter activity	2
intracellular signaling cassette	1
regulation of membrane potential	1
response to stress	1
response to decreased oxygen levels	1
heart development	1
animal organ morphogenesis	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
organelle organization	1
striated muscle tissue development	1
skeletal muscle organ development	1
macromolecule biosynthetic process	1
response to stimulus	1
fatty acid metabolic process	1
lipid oxidation	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to potassium ion	1
cellular response to metal ion	1
blood vessel diameter maintenance	1
response to reactive oxygen species	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to hormone	1
energy derivation by oxidation of organic compounds	1
regulation of blood pressure	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
cell population proliferation	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transmembrane signaling receptor activity	1

Protein interactions and networks

STRING

1716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC9	KCNJ8	Q15842	992
ABCC9	KCNJ11	Q14654	978
ABCC9	RBM20	Q5T481	805
ABCC9	SCN5A	Q14524	760
ABCC9	MYBPC3	Q14896	723
ABCC9	CSRP3	P50461	715
ABCC9	DSG2	Q14126	713
ABCC9	TMPO	P08918	707
ABCC9	EYA4	O95677	703
ABCC9	NEXN	Q0ZGT2	696
ABCC9	LDB3	O75112	690
ABCC9	TCAP	O15273	685
ABCC9	SGCD	Q92629	680
ABCC9	ACTN2	P35609	667
ABCC9	KCNE5	Q9UJ90	664

IntAct

5 interactions, top by confidence:

A	B	Type	Score
HSPB2	ABCC9	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
ABCC8	ABCC9	psi-mi:“MI:0914”(association)	0.350
ABCC9	KCNJ11	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (7): ABCC9 (Two-hybrid), ABCC9 (Two-hybrid), ABCC9 (Affinity Capture-Western), ABCC9 (Affinity Capture-MS), ABCC9 (Affinity Capture-MS), ABCC9 (Protein-RNA), ESF1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A059JK44, A0A0D1BUH6, A0A0S6XH62, A0A0U1LQE1, A0A142I732, A0A179H0T5, A0A348AXX9, A0A3G9H9H1, A0A8J9WHR9, A7A063, C8ZCR2, F2Q5G0, F2RPA4, F9X9V4, G4N2B5, I1R9B3, I1RF50, I1S2J9, K0E4D9, K3VYH8, O15440, O60706, P0CE68, P0CE70, P0CU83, P14772, P21441, P38735, P70170, P82451, P9WEL8, Q08D64, Q10185, Q2UPC0, Q4WA92, Q4WSI1, Q4WT65, Q5A762, Q5AV01, Q63563

Diamond homologs: A0A0D1CZ63, A0A0U1LQE1, A0A1U8QTJ9, A2XCD4, A7KVC2, B2RX12, E9Q236, F1M3J4, F9X9V4, G4N2B5, J9VQH1, O15438, O15439, O15440, O31708, O35379, O60706, O70127, O88269, O88563, O95255, P0CE69, P14772, P16875, P16877, P21439, P21440, P32386, P33527, P38735, P39109, P53049, P70170, P82451, P91660, P9WEL8, Q07QX6, Q08201, Q09427, Q0VQP5

SIGNOR signaling

1 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

2182 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	37
Uncertain significance	940
Likely benign	842
Benign	121

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1000443	NM_020297.4(ABCC9):c.2721T>G (p.Tyr907Ter)	Pathogenic
1022992	NM_020297.4(ABCC9):c.2371C>T (p.Gln791Ter)	Pathogenic
1026876	NM_020297.4(ABCC9):c.2422_2423del (p.Arg808fs)	Pathogenic
1035485	NM_020297.4(ABCC9):c.438del (p.Thr147fs)	Pathogenic
1044828	NM_020297.4(ABCC9):c.2826T>G (p.Tyr942Ter)	Pathogenic
1057737	NM_020297.4(ABCC9):c.2529_2530del (p.Ile844fs)	Pathogenic
1395006	NM_020297.4(ABCC9):c.1022_1032dup (p.Lys345fs)	Pathogenic
1402291	NM_020297.4(ABCC9):c.3269del (p.Gly1090fs)	Pathogenic
1409851	NM_020297.4(ABCC9):c.1319del (p.Gln440fs)	Pathogenic
1446144	NM_020297.4(ABCC9):c.1600del (p.Leu534fs)	Pathogenic
146315	GRCh38/hg38 12p12.3-12.1(chr12:15840854-22021652)x1	Pathogenic
1482842	NM_020297.4(ABCC9):c.1867G>T (p.Glu623Ter)	Pathogenic
1486684	NM_020297.4(ABCC9):c.1057_1073dup (p.Phe359_Leu360insTerPhe)	Pathogenic
1527688	GRCh37/hg19 12p12.3-11.23(chr12:17884992-26704895)	Pathogenic
1711337	NM_020297.4(ABCC9):c.3346C>G (p.Arg1116Gly)	Pathogenic
1712081	NM_020297.4(ABCC9):c.2444G>C (p.Gly815Ala)	Pathogenic
2004320	NM_020297.4(ABCC9):c.2625T>A (p.Tyr875Ter)	Pathogenic
2008293	NM_020297.4(ABCC9):c.2828C>G (p.Ser943Ter)	Pathogenic
2018281	NM_020297.4(ABCC9):c.1320+2T>G	Pathogenic
2018500	NM_020297.4(ABCC9):c.729del (p.Ile243fs)	Pathogenic
2022414	NM_020297.4(ABCC9):c.2589_2590del (p.Arg864fs)	Pathogenic
2023230	NM_020297.4(ABCC9):c.3586C>T (p.Gln1196Ter)	Pathogenic
2059714	NM_020297.4(ABCC9):c.565C>T (p.Arg189Ter)	Pathogenic
2081678	NM_020297.4(ABCC9):c.259dup (p.Ile87fs)	Pathogenic
2128352	NM_020297.4(ABCC9):c.3388_3389insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGAAAACTGGCTAGCCATATGTAGAAAGCTGAAACTGGATCCCTTCCTTACACCTTATACAAAAATCAAATCAATTCAAGATGGGATGATTTCTT (p.Tyr1130delinsPhePhePhePhePhePhePheXaaXaaXaaXaaLysLeuAlaSerHisMetTer)	Pathogenic
2167066	NM_020297.4(ABCC9):c.1219del (p.Glu407fs)	Pathogenic
265666	NM_020297.4(ABCC9):c.3460C>G (p.Arg1154Gly)	Pathogenic
2663857	NM_020297.4(ABCC9):c.2954A>C (p.Tyr985Ser)	Pathogenic
2832242	NM_020297.4(ABCC9):c.1108_1123del (p.Leu369_Gln370insTer)	Pathogenic
2842642	NM_020297.4(ABCC9):c.2099T>G (p.Leu700Ter)	Pathogenic

SpliceAI

5080 predictions. Top by Δscore:

Variant	Effect	Δscore
12:21805996:A:AC	donor_gain	1.0000
12:21805997:C:CC	donor_gain	1.0000
12:21805997:CAG:C	donor_gain	1.0000
12:21806165:AATC:A	donor_gain	1.0000
12:21807344:A:AC	donor_gain	1.0000
12:21807345:C:CC	donor_gain	1.0000
12:21815757:TCATA:T	donor_loss	1.0000
12:21815758:CATA:C	donor_loss	1.0000
12:21815759:ATAC:A	donor_loss	1.0000
12:21815760:TACC:T	donor_loss	1.0000
12:21815761:ACC:A	donor_loss	1.0000
12:21828956:ACCGT:A	donor_gain	1.0000
12:21828957:CCGTC:C	donor_gain	1.0000
12:21829056:CATGC:C	acceptor_gain	1.0000
12:21829057:ATGC:A	acceptor_gain	1.0000
12:21829058:TGC:T	acceptor_gain	1.0000
12:21829059:GC:G	acceptor_gain	1.0000
12:21829059:GCC:G	acceptor_loss	1.0000
12:21829060:CC:C	acceptor_gain	1.0000
12:21829061:C:CA	acceptor_loss	1.0000
12:21829061:C:CC	acceptor_gain	1.0000
12:21829062:T:A	acceptor_loss	1.0000
12:21838076:A:AC	donor_gain	1.0000
12:21838077:C:CC	donor_gain	1.0000
12:21838169:CC:C	acceptor_gain	1.0000
12:21838170:CC:C	acceptor_gain	1.0000
12:21838171:C:CC	acceptor_gain	1.0000
12:21852092:CTTA:C	donor_loss	1.0000
12:21852093:TTAC:T	donor_loss	1.0000
12:21852094:TAC:T	donor_loss	1.0000

AlphaMissense

10169 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:21807377:T:A	D1473V	1.000
12:21807377:T:G	D1473A	1.000
12:21807378:C:G	D1473H	1.000
12:21807428:A:G	L1456P	1.000
12:21814694:C:T	G1351E	1.000
12:21814695:C:A	G1351W	1.000
12:21818242:C:G	G1227R	1.000
12:21818242:C:T	G1227R	1.000
12:21828975:A:G	W1218R	1.000
12:21828975:A:T	W1218R	1.000
12:21838087:C:G	R1186P	1.000
12:21838103:C:G	G1181R	1.000
12:21838103:C:T	G1181R	1.000
12:21838165:A:G	L1160P	1.000
12:21852138:A:G	W910R	1.000
12:21852138:A:T	W910R	1.000
12:21852408:A:G	L868P	1.000
12:21852483:T:A	D843V	1.000
12:21852483:T:G	D843A	1.000
12:21852484:C:G	D843H	1.000
12:21852504:T:A	D836V	1.000
12:21852505:C:G	D836H	1.000
12:21861026:A:G	L790P	1.000
12:21872682:A:G	L714P	1.000
12:21872688:G:A	S712F	1.000
12:21872691:T:A	K711M	1.000
12:21872694:C:T	G710E	1.000
12:21872695:C:A	G710W	1.000
12:21872709:C:A	G705V	1.000
12:21872709:C:T	G705D	1.000

dbSNP variants (sampled 300 via entrez): RS1000001431 (12:21935217 T>C), RS1000035870 (12:21852163 G>A,T), RS1000050511 (12:21800939 CTG>C), RS1000056304 (12:21836579 G>A), RS1000076271 (12:21928237 A>G), RS1000087553 (12:21881541 A>T), RS1000107819 (12:21865371 G>A), RS1000107874 (12:21851610 C>G,T), RS1000123850 (12:21880733 A>T), RS1000151184 (12:21928795 A>G), RS1000168014 (12:21905742 C>G), RS1000192386 (12:21842147 T>C), RS1000209291 (12:21941367 C>A), RS1000211777 (12:21811916 T>C), RS1000214977 (12:21797024 G>T)

Disease associations

OMIM: gene MIM:601439 | disease phenotypes: MIM:608569, MIM:239850, MIM:614050, MIM:619719, MIM:601144, MIM:115195, MIM:607411, MIM:610253, MIM:115080, MIM:115200, MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrichotic osteochondrodysplasia Cantu type	Definitive	Autosomal dominant
dilated cardiomyopathy 1O	Strong	Autosomal dominant
intellectual disability and myopathy syndrome	Strong	Autosomal recessive
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
acromegaloid facial appearance syndrome	Supportive	Autosomal dominant
hypertrichosis-acromegaloid facial appearance syndrome	Supportive	Autosomal dominant
Brugada syndrome	Limited	Autosomal dominant
atrial fibrillation, familial, 12	Limited	Unknown

ClinGen Gene-Disease Validity (3)

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

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

Mondo (24): dilated cardiomyopathy 1O (MONDO:0012062), hypertrichotic osteochondrodysplasia Cantu type (MONDO:0009406), atrial fibrillation, familial, 12 (MONDO:0013545), intellectual disability and myopathy syndrome (MONDO:0859224), cardiomyopathy (MONDO:0004994), intellectual disability (MONDO:0001071), breast ductal adenocarcinoma (MONDO:0005590), dilated cardiomyopathy (MONDO:0005021), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), Brugada syndrome (MONDO:0015263), hypertrophic cardiomyopathy 2 (MONDO:0007266), patent ductus arteriosus (MONDO:0011827), Kleefstra syndrome 1 (MONDO:0027407), myocardial infarction (MONDO:0005068), ventricular tachycardia (MONDO:0005477)

Orphanet (15): Familial isolated dilated cardiomyopathy (Orphanet:154), Cantú syndrome (Orphanet:1517), Rare cardiomyopathy (Orphanet:167848), Dilated cardiomyopathy (Orphanet:217604), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Brugada syndrome (Orphanet:130), Kleefstra syndrome (Orphanet:261494), Hereditary progressive cardiac conduction defect (Orphanet:871), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Familial dilated cardiomyopathy (Orphanet:217607), Rare hypertrophic cardiomyopathy (Orphanet:217569), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), 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

125 total (30 of 125 shown, 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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001356_16	Gout	1.000000e-07
GCST001762_947	Obesity-related traits	5.000000e-06
GCST002430_1	Hippocampal sclerosis of aging	1.000000e-09
GCST004862_22	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST005146_53	Birth weight	1.000000e-07
GCST006629_35	Pulse pressure	7.000000e-20
GCST007269_121	Pulse pressure	2.000000e-14
GCST008363_121	Offspring birth weight	3.000000e-08
GCST90000025_1028	Appendicular lean mass	8.000000e-15
GCST90000026_13	Appendicular lean mass	4.000000e-06
GCST90000027_39	Appendicular lean mass	2.000000e-10

EFO canonical traits (7, from GWAS)

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 (17)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D004374	Ductus Arteriosus, Patent	C14.240.400.340; C14.280.400.340; C16.131.240.400.340
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009203	Myocardial Infarction	C14.280.647.500; C14.907.585.500; C23.550.513.355.750; C23.550.717.489.750
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C535655	Acromegaloid facial appearance syndrome (supp.)
C535572	Cantu syndrome (supp.)
C563906	Cardiomyopathy, Dilated, 1o (supp.)
C566171	Cardiomyopathy, Familial Hypertrophic, 2 (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)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 72,465 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1159	PINACIDIL ANHYDROUS	4	6,303
CHEMBL472	GLYBURIDE	4	53,236
CHEMBL631	PROPAFENONE	4	12,711
CHEMBL49035	CROMAKALIM	2	135
CHEMBL12531	CLAMIKALANT	2	80

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

PharmGKB clinical annotations

1 annotations.

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

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2307024	ABCC9		0.00	0
rs11046217	ABCC9		0.00	0
rs704212	ABCC9	3	2.00	1	montelukast
rs829074	ABCC9		0.00	0
rs11046238	ABCC9		0.00	0
rs11046209	ABCC9		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCC subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 13b [PMID: 19101153]	Positive	6.17	pEC50

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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression, decreases methylation	3
Acetaminophen	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression	2
Aflatoxin B1	decreases methylation, decreases expression	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
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
Cyclosporine	decreases expression	1
Aflatoxin M1	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)

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

Trial	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	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	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	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	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)