KCNA5

Summary

KCNA5 (potassium voltage-gated channel subfamily A member 5, HGNC:6224) is a protein-coding gene on chromosome 12p13.32, encoding Potassium voltage-gated channel subfamily A member 5 (P22460). Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.

Potassium channels represent the most complex class of voltage-gated ino channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, the function of which could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion. This gene is intronless, and the gene is clustered with genes KCNA1 and KCNA6 on chromosome 12. Defects in this gene are a cause of familial atrial fibrillation type 7 (ATFB7).

Source: NCBI Gene 3741 — RefSeq curated summary.

At a glance

• Gene–disease (curated): atrial fibrillation, familial, 7 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 597 total — 3 pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6224
Approved symbol	KCNA5
Name	potassium voltage-gated channel subfamily A member 5
Location	12p13.32
Locus type	gene with protein product
Status	Approved
Aliases	Kv1.5, HK2, HPCN1
Ensembl gene	ENSG00000130037
Ensembl biotype	protein_coding
OMIM	176267
Entrez	3741

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000252321

RefSeq mRNA: 1 — MANE Select: NM_002234 NM_002234

CCDS: CCDS8536

Canonical transcript exons

ENST00000252321 — 1 exons

Exon	Start	End
ENSE00000893118	5043879	5046788

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 96.56.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5134 / max 120.3897, expressed in 213 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123602	0.2006	110
123605	0.1357	80
123603	0.0725	30
123604	0.0702	39
123601	0.0345	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	96.56	gold quality
blood vessel layer	UBERON:0004797	93.28	gold quality
cardiac atrium	UBERON:0002081	92.19	gold quality
right atrium auricular region	UBERON:0006631	91.89	gold quality
right coronary artery	UBERON:0001625	91.79	gold quality
popliteal artery	UBERON:0002250	91.76	gold quality
tibial artery	UBERON:0007610	91.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.35	gold quality
aorta	UBERON:0000947	90.97	gold quality
choroid plexus epithelium	UBERON:0003911	90.62	gold quality
ascending aorta	UBERON:0001496	90.11	gold quality
thoracic aorta	UBERON:0001515	90.01	gold quality
left coronary artery	UBERON:0001626	89.93	gold quality
coronary artery	UBERON:0001621	89.91	gold quality
descending thoracic aorta	UBERON:0002345	89.04	gold quality
mucosa of stomach	UBERON:0001199	88.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.35	gold quality
saphenous vein	UBERON:0007318	80.72	gold quality
myocardium	UBERON:0002349	79.75	gold quality
endothelial cell	CL:0000115	79.26	silver quality
heart	UBERON:0000948	78.38	gold quality
vena cava	UBERON:0004087	77.60	silver quality
islet of Langerhans	UBERON:0000006	76.17	gold quality
mucosa of urinary bladder	UBERON:0001259	76.12	gold quality
diaphragm	UBERON:0001103	75.84	gold quality
apex of heart	UBERON:0002098	75.04	gold quality
nucleus accumbens	UBERON:0001882	73.78	gold quality
pituitary gland	UBERON:0000007	73.13	gold quality
pigmented layer of retina	UBERON:0001782	72.06	gold quality
hypothalamus	UBERON:0001898	72.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	14.11
E-ENAD-27	no	7.62
E-ANND-3	no	1.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, HIF1A, HSF1, SP1

miRNA regulators (miRDB)

65 targeting KCNA5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4719	99.73	72.10	3329

Literature-anchored findings (GeneRIF, showing 40)

• characterization of a truncated form of Kv1.5 (PMID:12021261)
• Modulation by protein kinase C activation: role of the Kvbeta1.2 subunit. (PMID:12130714)
• co-localization of Kv1.5 with PSD95 at the cell surface is similarly independent of the canonical PDZ-binding motif (PMID:12435606)
• Reduction in the activation energy for the inactivation transition from the open state underlies the inhibition of hKv1.5 Na(+) current at low pH. (PMID:12601085)
• Kv1.5 potassium channel mRNA expression correlates with glioma entities and malignancy grades; expression is high in astrocytomas, moderate in oligodendrogliomas, and low in glioblastomas. (PMID:12850541)
• multiple isoforms of SAP97 were identifed in human heart atrium specimens; isoforms were found to co-immunoprecipiate with hKv1.5; isoforms were found to have distinct effect on hKv1.5 current and spatial channel organization (PMID:12970345)
• the destabilization or bending of the S6 alpha-helix of KV1.5 caused by the PXP motif apparently creates a flexible “hinge” that allows movement of the lower S6 segment during channel gating and opening (PMID:13679372)
• No electrical remodeling is evident in Kv1.5DN-expressing ventricular myocytes, and the (Kv1.5DN-induced) elimination of IK,slow1 does not result in spontaneous ventricular arrhythmias. (PMID:14527939)
• an examination of the effect of K channel blocker S0100176) on the structure of the Kv1.5 channel (PMID:14578345)
• Overexpression of the human KCNA5 gene increases K+ currents (i.e., K+ efflux or loss), accelerates apoptotic volume decrease (AVD), increases caspase-3 activity, and induces apoptosis (PMID:15140747)
• Heterologously expressed human pulmonary arterial smooth muscle cells (PASMC) Kv1.5 generated an O2- and correolide-sensitive I(K) like that in resistance PASMCs. (PMID:15217912)
• There is a central role for developmentally regulated ductus arteriosus SMC O2-sensitive Kv channels in the functional closure of the DA. (PMID:15353504)
• This suggests that for Kv channels, the coupling between voltage sensing and gating reflects primarily an intrasubunit interaction. (PMID:15623896)
• P. 142: “An aligment of KCNA5 among human, mouse, and rat shows 86% amino acid identity, and no monogenicc human arrhythmia syndrome has been linked to KCNA5” (PMID:15735608)
• a pathway for Kv1.5 internalization from the cell surface involving early endosomes, followed by later trafficking by the dynein motor along microtubules. (PMID:16051887)
• KCNA5 is an important Kv channel that regulates resting membrane potential and that acute hypoxia selectively reduces KCNA5 channel activity in pulmonary smooth muscle cells relative to mesenteric smooth muscle cells and other cell types. (PMID:16236819)
• We found three heterozygous SNPs: R87Q, A251T, and P307S. Both R87Q and P307S diminished the inactivation amplitude. (PMID:16411137)
• specific inhibition of kinase C by Calphostin C eliminated the increase in wild-type hKv1.5 currents associated with synapse-associated protein 97 overexpression suggesting a role for this kinase in the response (PMID:16466689)
• functional role of K(v)1.5 and K(v)1.3 on activated human dendritic cells (PMID:16729292)
• hKv1.5 channel is expressed in human alveolar macrophages and it plays a role in phagocytosis and migration of the human alveolar macrophage. (PMID:16765315)
• Mg2+ block causes voltage-dependent inactivation of Kv1.5 (PMID:16902793)
• These results imply that protonation of residue 463 does not modulate inactivation solely by an electrostatic interaction with residues near the pore mouth. (PMID:16956964)
• results suggest Kv1.5 channels are modulated by agonists; novel SNPs are present in idiopathic pulmonary arterial hypertension; SNPs may underlie altered expression and/or function of Kv1.5 channels in pulmonary artery smooth muscle cells in IPAH (PMID:17267549)
• S-acylation can regulate steady-state expression of Kv1.5. (PMID:17344312)
• Down-regulation of Kv1.5 enhanced the drug-resistant phenotype of gastric cancer cells. (PMID:17428690)
• In conclusion, N-cadherin modifies Kv1.5 channel activity and is thus a novel candidate signaling molecule participating in the regulation of a variety of functions including cardiac action potential and vascular tone. (PMID:17868645)
• mitochondrial abnormalities that disturb the reactive O(2) species HIF-1alpha-Kv1.5 O(2)-sensing pathway contribute to the pathogenesis of pulmonary arterial hypertension and cancer–REVIEW (PMID:18083891)
• KCNA5 is involved K(+)-channel in regulatory volume decrease in human spermatozoa, and channel activity is regulated beyond the extent of protein expression. (PMID:18157847)
• R87Q and P307S polymorphisms in hKv1.5, possibly in combination with other risk factors, may influencethe development of postoperative atrial fibrillation (PMID:18209767)
• implicate the traffic and localization of Kv1.3/Kv1.5 heteromers in the complex regulation of immune system cells (PMID:18218624)
• SAP97 regulates the K(+) current in cardiac myocytes by retaining and immobilizing Kv1.5 subunits in the plasma membrane. (PMID:18245566)
• Results support a role of FHL1 as a key molecular component in the I(Kur) complex in human atrium, where it likely regulates functional expression of KCNA5. (PMID:18281375)
• Report a Kv1.5 channel with an altered activation gate sequence that displays both “fast” and “slow” activation kinetics. (PMID:18385285)
• Active site architecture, certain key residues and pharmacophore common-features responsible for substrate specificity are identified on Kv1.5 potassium channel that are very helpful in understanding the blockade mechanism of Kv1.5 potassium channel. (PMID:18485768)
• The Rab GTPases thus constitute dynamic targets by which cells may modulate Kv1.5 functional expression. (PMID:18755741)
• Double-mutant cycle analysis indicates that R5 of Kvbeta1.3 interacts with A501 and T480 of Kv1.5, residues located deep within the pore of the channel. (PMID:18987637)
• Replacing L45 and S6(T) by corresponding hKv2.1 sequences, transfered the hKv2.1 kinetics but not the voltage dependence to hKv1.5. Point mutations in S6(T) show that it needs to be alpha-helical and forms a “crevice” for the L45 residues I422 and T426. (PMID:19029374)
• In the absence of potassium ion, significant N-methyl-D-glucamine (NMDG)-positive currents could be recorded from human embryonic kidney cells expressing Kv3.1 or Kv3.2b channels and Kv1.5 Arg487Tyr/Val, but not wild-type channels. (PMID:19332619)
• These findings expand the spectrum of mutations in KCNA5 linked to atrial fibrillation (AF) and provide new insight into the molecular mechanism involved in AF. (PMID:19343045)
• Antiarrhythmic drug-induced internalization of the atrial-specific k+ channel kv1.5. (PMID:19443837)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcna5	ENSMUSG00000045534
rattus_norvegicus	Kcna5	ENSRNOG00000072038

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNV2 (ENSG00000168263), KCNG4 (ENSG00000168418), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily A member 5 — P22460 (reviewed: P22460)

Alternative names: HPCN1, Voltage-gated potassium channel HK2, Voltage-gated potassium channel subunit Kv1.5

All UniProt accessions (1): P22460

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. Homotetrameric channels display rapid activation and slow inactivation. Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2. May play a role in regulating the secretion of insulin in normal pancreatic islets. Exhibits a faster depolarization rate, reduced voltage-dependent recovery from inactivation and an excessive cumulative inactivation.

Subunit / interactions. Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3. Interacts with KCNAB1. Interacts with UBE2I. Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart.

Subcellular location. Cell membrane.

Tissue specificity. Pancreatic islets and insulinoma.

Post-translational modifications. Glycosylated. Sumoylated on Lys-221, and Lys-536, preferentially with SUMO3. Sumoylation regulates the voltage sensitivity of the channel.

Disease relevance. Atrial fibrillation, familial, 7 (ATFB7) [MIM:612240] 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.

Activity regulation. Inhibited by 4-aminopyridine, nicotine, bepridil, correolide, and endothelin-1.

Domain organisation. The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments. The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.

Similarity. Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P22460-1	1	yes
P22460-2	2, Short

RefSeq proteins (1): NP_002225* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003972	K_chnl_volt-dep_Kv1	Family
IPR004052	K_chnl_volt-dep_Kv1.5	Family
IPR005821	Ion_trans_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family

Pfam: PF00520, PF02214

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (64 total): sequence variant 15, topological domain 8, sequence conflict 8, transmembrane region 6, region of interest 6, mutagenesis site 5, compositionally biased region 4, intramembrane region 2, repeat 2, short sequence motif 2, cross-link 2, chain 1, modified residue 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22460-F1	72.64	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 557, 346, 221, 536

Mutagenesis-validated functional residues (5):

Position	Phenotype
15	loss of dlg1 effect on channel current.
220	reduces sumoylation; when associated with n-535.
221	abolishes sumoylation; when associated with r-536.
535	reduces sumoylation; when associated with n-220.
536	abolishes sumoylation; when associated with r-221.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-5576890	Phase 3 - rapid repolarisation
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 809 (showing top): AHRARNT_01, GOBP_POTASSIUM_ION_TRANSPORT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_BUNDLE_OF_HIS_CELL_TO_PURKINJE_MYOCYTE_COMMUNICATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_POTASSIUM_CHANNELS

GO Biological Process (28): action potential (GO:0001508), response to hypoxia (GO:0001666), potassium ion transport (GO:0006813), Notch signaling pathway (GO:0007219), response to mechanical stimulus (GO:0009612), regulation of vasoconstriction (GO:0019229), regulation of membrane potential (GO:0042391), response to hydrogen peroxide (GO:0042542), regulation of insulin secretion (GO:0050796), protein homooligomerization (GO:0051260), negative regulation of cytosolic calcium ion concentration (GO:0051481), potassium ion homeostasis (GO:0055075), response to hyperoxia (GO:0055093), membrane hyperpolarization (GO:0060081), regulation of atrial cardiac muscle cell membrane repolarization (GO:0060372), potassium ion transmembrane transport (GO:0071805), atrial cardiac muscle cell action potential (GO:0086014), membrane repolarization during bundle of His cell action potential (GO:0086050), membrane repolarization during SA node cell action potential (GO:0086052), regulation of heart rate by cardiac conduction (GO:0086091), potassium ion export across plasma membrane (GO:0097623), membrane repolarization during atrial cardiac muscle cell action potential (GO:0098914), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of myoblast proliferation (GO:2000288), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), protein complex oligomerization (GO:0051259), transmembrane transport (GO:0055085)

GO Molecular Function (13): signaling receptor binding (GO:0005102), voltage-gated potassium channel activity (GO:0005249), delayed rectifier potassium channel activity (GO:0005251), outward rectifier potassium channel activity (GO:0015271), protein kinase binding (GO:0019901), alpha-actinin binding (GO:0051393), voltage-gated potassium channel activity involved in bundle of His cell action potential repolarization (GO:0086087), voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization (GO:0086089), voltage-gated potassium channel activity involved in SA node cell action potential repolarization (GO:0086090), scaffold protein binding (GO:0097110), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (13): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), cell surface (GO:0009986), intercalated disc (GO:0014704), membrane (GO:0016020), Z disc (GO:0030018), potassium channel complex (GO:0034705), membrane raft (GO:0045121), intracellular canaliculus (GO:0046691), perinuclear region of cytoplasm (GO:0048471), caveola (GO:0005901), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Potassium Channels	1
Cardiac conduction	1
Neuronal System	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization	3
regulation of membrane potential	2
response to stress	2
regulation of biological quality	2
membrane repolarization during cardiac muscle cell action potential	2
protein binding	2
voltage-gated potassium channel activity	2
cytoplasm	2
response to decreased oxygen levels	1
metal ion transport	1
cell surface receptor signaling pathway	1
response to external stimulus	1
response to abiotic stimulus	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
monoatomic ion transmembrane transport	1
response to reactive oxygen species	1
insulin secretion	1
regulation of protein secretion	1
regulation of peptide hormone secretion	1
protein complex oligomerization	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
response to increased oxygen levels	1
regulation of cardiac muscle cell membrane repolarization	1
atrial cardiac muscle cell membrane repolarization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
cardiac muscle cell action potential involved in contraction	1
atrial cardiac muscle cell to AV node cell signaling	1
bundle of His cell action potential	1
SA node cell action potential	1
regulation of heart rate	1
cardiac conduction	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
kinase binding	1
actinin binding	1

Protein interactions and networks

STRING

1914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNA5	KCNAB1	Q14722	950
KCNA5	KCNA2	P16389	942
KCNA5	KCNE2	Q9Y6J6	872
KCNA5	KCNH2	Q12809	862
KCNA5	DLG1	Q12959	861
KCNA5	KCNAB2	Q13303	857
KCNA5	KCNAB3	O43448	836
KCNA5	SCN5A	Q14524	827
KCNA5	KCNIP2	Q9NS61	815
KCNA5	TPI1	P00938	802
KCNA5	KCNE1	P15382	709
KCNA5	KCNJ8	Q15842	707
KCNA5	KCNK3	O14649	705
KCNA5	KCNJ3	P48549	703
KCNA5	KCNJ2	P48049	684

IntAct

263 interactions, top by confidence:

A	B	Type	Score
KCNA5	SCRIB	psi-mi:“MI:0915”(physical association)	0.610
DLG1	KCNA5	psi-mi:“MI:0915”(physical association)	0.610
KCNA5	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.610
KCNA5	DLG1	psi-mi:“MI:0407”(direct interaction)	0.610
KCNA5	TMEM107	psi-mi:“MI:0915”(physical association)	0.560
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
KCNA5	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SNTB2	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	KCNA5	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF2	KCNA5	psi-mi:“MI:0407”(direct interaction)	0.440
RHPN1	KCNA5	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI3	KCNA5	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF12	KCNA5	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	LIMK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (111): KCNA5 (Reconstituted Complex), KCNA5 (Biochemical Activity), STUB1 (Affinity Capture-Western), KCNA5 (Affinity Capture-Western), HSPA8 (Affinity Capture-Western), KCNA5 (Affinity Capture-Western), KCNA3 (Affinity Capture-MS), NPHP1 (Affinity Capture-MS), KCNA5 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), GOLM1 (Affinity Capture-MS), DOLK (Affinity Capture-MS)

ESM2 similar proteins: A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, D4ADX7, O35173, O35174, O88758, P15384, P15388, P16390, P17658, P17659, P19024, P22001, P22460, P22462, P25122, P48547, P50638, P59053, P59994, P79197, Q03719, Q03721, Q14B80, Q17ST2, Q61762, Q61923, Q63734, Q7TSH7, Q8CFS6, Q8R1C0

Diamond homologs: A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16389, P16390, P17970, P19024, P22001, P22459, P22460, P22462, P25122, P48547, P50638, P59053, P59994

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
AMPK	“down-regulates activity”	KCNA5	phosphorylation
PRKAA1	“down-regulates activity”	KCNA5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Tight junction interactions	6	29.5×	4e-06
Assembly and cell surface presentation of NMDA receptors	8	27.1×	7e-08
Neurexins and neuroligins	10	26.2×	1e-09
Protein-protein interactions at synapses	5	17.7×	2e-04
SUMOylation of transcription cofactors	5	16.2×	2e-04
Signaling by Rho GTPases	9	4.1×	3e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	9	4.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	13	69.3×	7e-19
protein localization to synapse	6	42.2×	6e-07
receptor clustering	7	40.1×	7e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	27.3×	6e-06
establishment or maintenance of cell polarity	6	22.1×	2e-05
bicellular tight junction assembly	5	15.2×	7e-04
Rho protein signal transduction	5	11.4×	2e-03
protein-containing complex assembly	10	10.4×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	431
Likely benign	112
Benign	14

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
127137	NM_002234.4(KCNA5):c.143A>G (p.Glu48Gly)	Pathogenic
13469	NM_002234.4(KCNA5):c.1123G>T (p.Glu375Ter)	Pathogenic
13472	NM_002234.4(KCNA5):c.1828G>A (p.Glu610Lys)	Pathogenic

SpliceAI

4 predictions. Top by Δscore:

Variant	Effect	Δscore
12:5044086:GC:G	donor_gain	0.3000
12:5044084:GAGC:G	donor_gain	0.2100
12:5045495:A:AG	acceptor_gain	0.2000
12:5045496:G:GG	acceptor_gain	0.2000

AlphaMissense

3973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:5045150:T:C	F335L	1.000
12:5045152:C:A	F335L	1.000
12:5045152:C:G	F335L	1.000
12:5045383:G:C	K412N	1.000
12:5045383:G:T	K412N	1.000
12:5045385:T:C	L413P	1.000
12:5045406:T:C	L420P	1.000
12:5045448:T:C	L434P	1.000
12:5045489:T:C	F448L	1.000
12:5045491:C:A	F448L	1.000
12:5045491:C:G	F448L	1.000
12:5045495:A:C	S450R	1.000
12:5045497:T:A	S450R	1.000
12:5045497:T:G	S450R	1.000
12:5045561:T:A	W472R	1.000
12:5045561:T:C	W472R	1.000
12:5045564:T:A	W473R	1.000
12:5045564:T:C	W473R	1.000
12:5045566:G:C	W473C	1.000
12:5045566:G:T	W473C	1.000
12:5045591:G:C	G482R	1.000
12:5045592:G:A	G482D	1.000
12:5045597:G:T	G484W	1.000
12:5045598:G:A	G484E	1.000
12:5045598:G:T	G484V	1.000
12:5045610:C:A	P488H	1.000
12:5045636:G:C	G497R	1.000
12:5045637:G:A	G497D	1.000
12:5045645:T:C	C500R	1.000
12:5045646:G:A	C500Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000040930 (12:5041992 C>T), RS1001365251 (12:5043012 T>C), RS1001489344 (12:5043082 C>G), RS1001994004 (12:5043688 C>T), RS1003032973 (12:5044142 C>A,G,T), RS1003104758 (12:5043943 G>A,T), RS1003591437 (12:5044377 C>G), RS1004890199 (12:5042699 T>A), RS1005224382 (12:5043917 G>A), RS1005838107 (12:5046909 G>A), RS1007066249 (12:5046177 C>A,G,T), RS1007150347 (12:5043994 C>T), RS1007168973 (12:5041908 T>C), RS1007219827 (12:5042221 C>G,T), RS1008775209 (12:5046305 T>A)

Disease associations

OMIM: gene MIM:176267 | disease phenotypes: MIM:612240, MIM:178600, MIM:601144

GenCC curated gene-disease

Disease	Classification	Inheritance
atrial fibrillation, familial, 7	Moderate	Autosomal dominant
familial atrial fibrillation	Supportive	Autosomal dominant

Mondo (8): atrial fibrillation, familial, 7 (MONDO:0012828), third-degree atrioventricular block (MONDO:0000468), pulmonary hypertension, primary, 1 (MONDO:0024533), pulmonary arterial hypertension (MONDO:0015924), Brugada syndrome 1 (MONDO:0011001), heart disorder (MONDO:0005267), cardiac rhythm disease (MONDO:0007263), familial atrial fibrillation (MONDO:0018054)

Orphanet (3): Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422), Pulmonary arterial hypertension (Orphanet:182090), Brugada syndrome (Orphanet:130)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001279	Syncope
HP:0001658	Myocardial infarction
HP:0001688	Sinus bradycardia
HP:0001727	Thromboembolic stroke
HP:0001907	Thromboembolism
HP:0001962	Palpitations
HP:0002094	Dyspnea
HP:0002321	Vertigo
HP:0003546	Exercise intolerance
HP:0003596	Middle age onset
HP:0004754	Permanent atrial fibrillation
HP:0004757	Paroxysmal atrial fibrillation
HP:0005110	Atrial fibrillation
HP:0005184	Prolonged QTc interval
HP:0006699	Premature atrial contractions
HP:0012248	Prolonged PR interval
HP:0012378	Fatigue
HP:0025708	Early young adult onset
HP:0025710	Late young adult onset
HP:0100749	Chest pain

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006658_2	Longevity	2.000000e-06
GCST012490_350	Femur bone mineral density x serum urate levels interaction	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006331	Heart Diseases	C14.280
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C567389	Atrial Fibrillation, Familial, 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2362996 (PROTEIN FAMILY), CHEMBL4306 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 165,592 (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
CHEMBL1201729	DRONEDARONE HYDROCHLORIDE	4	587
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL2107383	VERNAKALANT HYDROCHLORIDE	4	115
CHEMBL652	FLECAINIDE	4	9,582
CHEMBL4094440	BMS-919373	2	28
CHEMBL602070	BMS-394136	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Voltage-gated potassium channels (K_v)

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
DPO-1	Channel blocker	7.3	pIC50
clofilium	Channel blocker	6.9	pIC50
S9947	Channel blocker	6.4	pIC50
dronedarone	Inhibition	5.63	pIC50
bupivacaine	Channel blocker	5.4	pKd
quinidine	Channel blocker	5.2	pKd
resiniferatoxin	Channel blocker	4.6	pKd
propafenone	Channel blocker	4.4	pIC50
nifedipine	Channel blocker	4.1	pKd
flecainide	Channel blocker	4.0	pKd
diltiazem	Pore blocker	3.9	pKd
fampridine	Pore blocker	3.6	pKd

Binding affinities (BindingDB)

15 measured of 15 human assays (15 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-methyl-3-[3-[2-pyridin-3-ylethyl(pyridin-4-ylmethyl)amino]propoxy]quinolin-2-one	IC50	300 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
1-ethyl-6-[3-[2-pyridin-3-ylethyl(pyridin-4-ylmethyl)amino]propoxy]quinolin-2-one	IC50	320 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
6-[5-[bis(pyridin-3-ylmethyl)amino]pentoxy]-1-methylquinolin-2-one	IC50	510 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
1-methyl-6-[5-[3-phenylpropyl(pyridin-3-yl)amino]pentoxy]quinolin-2-one	IC50	600 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
1-ethyl-3,3,5-trimethyl-7-[3-[2-(2-methyl-4-oxofuro[3,2-c]pyridin-5-yl)ethyl-(pyridin-4-ylmethyl)amino]propyl]-1,5-benzodiazepine-2,4-dione	IC50	620 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
1-ethyl-7-[[[2-(methoxymethyl)-3-pyridinyl]methyl-[2-(2-methyl-4-oxofuro[3,2-c]pyridin-5-yl)ethyl]amino]methyl]-3,3,5-trimethyl-1,5-benzodiazepine-2,4-dione	IC50	630 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
1-methyl-6-[5-[3-phenylpropyl(pyridin-3-ylmethyl)amino]pentoxy]quinolin-2-one	IC50	810 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
N-[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-1,5-benzodiazepin-7-yl)methyl]-2-(1-methylindol-3-yl)-N-(2-pyridin-3-ylethyl)acetamide	IC50	860 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
6-[3-[2-pyridin-3-ylethyl(pyridin-4-ylmethyl)amino]propoxy]-3,4-dihydro-2H-isoquinolin-1-one	IC50	940 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
N-[5-(1-methyl-2-oxoquinolin-6-yl)oxypentyl]-N-(2-pyridin-3-ylethyl)pyridine-3-carboxamide	IC50	1400 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
N-methyl-N-[2-[3-(1-methyl-2-oxoquinolin-6-yl)oxypropyl-(pyridin-4-ylmethyl)amino]ethyl]benzamide	IC50	1700 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
1-ethyl-7-[[[2-(methoxymethyl)-3-pyridinyl]methyl-[2-(7-methyl-4-oxofuro[3,2-c]pyridin-5-yl)ethyl]amino]methyl]-3,3,5-trimethyl-1,5-benzodiazepine-2,4-dione	IC50	2900 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
CHEMBL4539540	IC50	3400 nM
CHEMBL4474540	IC50	5600 nM
1-methyl-6-[3-[2-pyridin-2-ylethyl(pyridin-4-ylmethyl)amino]propoxy]quinolin-2-one	IC50	6300 nM	US-9212187: Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation

ChEMBL bioactivities

795 potent at pChembl≥5 of 850 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Ki	0.15	nM	CHEMBL5722941
9.74	IC50	0.18	nM	CHEMBL5722941
8.11	IC50	7.7	nM	CHEMBL1256851
8.05	IC50	9	nM	CHEMBL4065169
8.00	EC50	10	nM	CHEMBL3961395
8.00	EC50	10	nM	CHEMBL3940526
7.96	IC50	11	nM	CHEMBL4065169
7.96	IC50	11	nM	CHEMBL4104525
7.92	EC50	12	nM	CHEMBL3960875
7.82	IC50	15	nM	CHEMBL571976
7.70	EC50	20	nM	CHEMBL3899148
7.68	IC50	21	nM	CHEMBL216281
7.66	IC50	22	nM	CHEMBL3298226
7.64	IC50	23	nM	CHEMBL3298228
7.64	IC50	23	nM	CHEMBL4085436
7.62	IC50	24	nM	CHEMBL3356073
7.60	IC50	25	nM	CHEMBL3356073
7.60	EC50	25	nM	CHEMBL3930613
7.58	IC50	26	nM	CHEMBL4105245
7.55	IC50	28	nM	CHEMBL3622361
7.54	IC50	29	nM	CHEMBL4104525
7.52	IC50	30	nM	CHEMBL3622355
7.52	IC50	30	nM	CHEMBL4062996
7.52	IC50	30	nM	CHEMBL567671
7.52	IC50	30	nM	CHEMBL1088844
7.50	IC50	32	nM	CHEMBL3623054
7.48	IC50	33	nM	CHEMBL4075394
7.48	IC50	33	nM	CHEMBL288131
7.47	IC50	34	nM	CHEMBL3356074
7.47	IC50	34	nM	CHEMBL3622346
7.44	IC50	36	nM	CHEMBL385809
7.43	IC50	37	nM	CHEMBL2331989
7.40	IC50	40	nM	CHEMBL4521294
7.39	IC50	41	nM	CHEMBL4095750
7.37	IC50	43	nM	CHEMBL3298140
7.35	EC50	45	nM	CHEMBL444449
7.35	EC50	45	nM	CHEMBL3899683
7.34	IC50	46	nM	BMS-919373
7.34	IC50	46	nM	CHEMBL260684
7.33	IC50	47	nM	CHEMBL3623053
7.32	IC50	48	nM	CHEMBL2331990
7.32	IC50	48	nM	CHEMBL567235
7.30	EC50	50	nM	CHEMBL3958206
7.30	IC50	50	nM	CHEMBL4532101
7.30	IC50	50	nM	CHEMBL4450487
7.30	IC50	50	nM	CHEMBL288131
7.30	IC50	50	nM	BMS-394136
7.28	IC50	52	nM	CHEMBL3622360
7.28	IC50	52	nM	CHEMBL3623052
7.28	EC50	52	nM	CHEMBL3982686

PubChem BioAssay actives

705 with measured affinity, of 1302 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
3-[(1R,2aS,4S,5aS,8aS,10S,11aR,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,87R,93S,96S,99S)-17a,20a,23a,53a,63-pentakis(4-aminobutyl)-31-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-16,29a,72,78-tetrakis(2-amino-2-oxoethyl)-14a,26a-bis(3-amino-3-oxopropyl)-2a,38a,66-tribenzyl-28,50a,57-tris[(2S)-butan-2-yl]-4,5a,19,42,45,69-hexakis(3-carbamimidamidopropyl)-51,54-bis(2-carboxyethyl)-56a,99-bis(carboxymethyl)-36-[[(2S,3S)-1-(carboxymethylamino)-3-methyl-1-oxopentan-2-yl]carbamoyl]-39,60-bis[(1R)-1-hydroxyethyl]-75,93-bis(hydroxymethyl)-32a,35a,59a-tris[(4-hydroxyphenyl)methyl]-22-(1H-imidazol-4-ylmethyl)-96-(1H-indol-3-ylmethyl)-41a-methyl-25-(2-methylpropyl)-1a,3,4a,6,7a,9,10a,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,5,6a,8,9a,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.010,14.0144,148]nonahexacontahectan-8a-yl]propanoic acid	2198828: Binding affinity to KV channel (unknown origin) assessed as inhibition constant	ki	0.0001	uM
4-(4-phenylbutoxy)furo[3,2-g]chromen-7-one	2136237: Inhibition of Kv1.5 (unknown origin)	ic50	0.0077	uM
N-[6-[(1S)-1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]-2-pyridinyl]methanesulfonamide	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0090	uM
(1R)-1-[2-(3,5-dichlorophenyl)-3-pyridinyl]-2,2-dipyridin-3-ylethanol	1437177: Inhibition of Kv1.5 mediated ultra-rapid delayed rectifier current Ikur in human atrial myocytes by voltage-patch clamp electrophysiology method	ic50	0.0110	uM
7-(3,4-dichlorophenyl)-6-(5-fluoro-1-methylbenzimidazol-2-yl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	449154: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0150	uM
[(E)-(2,3-diethyl-1-methyl-6,7-dihydro-5H-indol-4-ylidene)amino] N-phenylcarbamate	274083: Inhibition of Kv1.5 expressed in LTK- cells by whole cell patch clamp assay	ic50	0.0210	uM
8-methoxy-N-(2-methyl-2-phenylpropyl)isoquinolin-1-amine	1224174: Inhibition of human Kv1.5 expressed in mouse L929 cells assessed as inhibition of current	ic50	0.0220	uM
5-methoxy-4-[(2-methyl-2-phenylpropyl)amino]-1H-quinazolin-2-one	1224174: Inhibition of human Kv1.5 expressed in mouse L929 cells assessed as inhibition of current	ic50	0.0230	uM
2-(2-chlorophenyl)-3-(2,2-dipyridin-3-ylethyl)pyridine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0230	uM
4-methoxy-N-(2-methyl-2-phenylpropyl)-1,2-benzothiazol-3-amine	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0240	uM
2-chloro-3-[2-[2-(2-chlorophenyl)-3-pyridinyl]-1-pyridin-3-ylethyl]pyridine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0260	uM
2,2,2-trifluoroethyl N-[4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexyl]carbamate	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0280	uM
7-(3,4-dichlorophenyl)-6-(5-fluoro-1-methylbenzimidazol-2-yl)-5-(methoxymethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine	449154: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0300	uM
[4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexyl] N-[4-(dimethylamino)phenyl]carbamate	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0300	uM
[[(1S,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]-phenylphosphoryl]benzene	476474: Inhibition of human Kv1.5 channel expressed in CHO cells by whole cell patch clamp assay	ic50	0.0300	uM
2-(3-chlorophenyl)-3-(2,2-dipyridin-3-ylethyl)pyridine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0300	uM
4-methoxy-1,1-dioxo-N-[[1-phenyl-4-(tetrazol-1-yl)cyclohexyl]methyl]-1,2-benzothiazol-3-imine	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0320	uM
N-[(2R,3R)-3-[(4-ethylphenyl)sulfonylamino]-2-hydroxy-2,3-dihydro-1H-inden-5-yl]-3-methoxybenzamide	290686: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0330	uM
3-(2,2-dipyridin-3-ylethyl)-2-[3-(trifluoromethoxy)phenyl]pyridine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0330	uM
4-methoxy-3-(2-methyl-2-phenylpropyl)iminoisoindol-1-one	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0340	uM
4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexan-1-ol	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0340	uM
4-[3-(2-fluorophenyl)propanoylamino]-3-phenyl-N,N-di(propan-2-yl)-2-pyridin-3-ylbutanamide	274038: Inhibition of Kv1.5	ic50	0.0360	uM
(7R)-6-(2-cyclopentyl-1,2,4-triazol-3-yl)-7-(3,4-dichlorophenyl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	730777: Antagonist activity at human Kv1.5 expressed in mouse L929 cells assessed as inhibition of delayed rectifier repolarization current by patch clamp assay	ic50	0.0370	uM
5-phenyl-2-pyridin-4-yl-N-(pyridin-2-ylmethyl)quinazolin-4-amine	1630993: Inhibition of human Kv1.5 transfected in mouse LTK cells	ic50	0.0400	uM
3-(2,2-dipyridin-3-ylethyl)-2-(3-methoxyphenyl)pyridine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0410	uM
4-methoxy-N-(2-methyl-2-phenylpropyl)-1,2-benzoxazol-3-amine	1224174: Inhibition of human Kv1.5 expressed in mouse L929 cells assessed as inhibition of current	ic50	0.0430	uM
N-[(8S)-8-[(4-ethylphenyl)sulfonylamino]-5,6,7,8-tetrahydronaphthalen-2-yl]-N-[(6-methyl-2-pyridinyl)methyl]-3-phenylpropanamide	329660: Inhibition of human Kv1.5 channel expressed in mouse L929 cells assessed as blockade of ultra rapidly activating potassium current by voltage clamp technique	ic50	0.0460	uM
5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide	1447683: Inhibition of recombinant human Kv1.5 expressed in mouse L929 cells by patch clamp assay	ic50	0.0460	uM
N-[4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexyl]pyrimidin-2-amine	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0470	uM
7-(3,4-dichlorophenyl)-6-(5-fluoro-1-propylbenzimidazol-2-yl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	449154: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0480	uM
(7R)-6-(2-cyclobutyl-1,2,4-triazol-3-yl)-7-(3,4-dichlorophenyl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	730777: Antagonist activity at human Kv1.5 expressed in mouse L929 cells assessed as inhibition of delayed rectifier repolarization current by patch clamp assay	ic50	0.0480	uM
[(7R)-7-(3,4-dichlorophenyl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl]-[(2S)-2-(4-fluorophenyl)pyrrolidin-1-yl]methanone	457613: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0500	uM
5-phenyl-4-(pyridin-2-ylmethylamino)quinazoline-2-carbonitrile	1630993: Inhibition of human Kv1.5 transfected in mouse LTK cells	ic50	0.0500	uM
5-phenyl-N-(pyridin-2-ylmethyl)-2-(1,3-thiazol-5-yl)quinazolin-4-amine	1630993: Inhibition of human Kv1.5 transfected in mouse LTK cells	ic50	0.0500	uM
propan-2-yl N-[4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexyl]carbamate	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0520	uM
3-[[4-(diethylsulfamoylamino)-1-phenylcyclohexyl]methylimino]-4-methoxy-1,1-dioxo-1,2-benzothiazole	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0520	uM
ethyl N-[4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexyl]carbamate	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0550	uM
6-[1-pyridin-3-yl-2-[2-[3-(trifluoromethyl)phenyl]-3-pyridinyl]ethyl]pyridin-2-amine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0560	uM
6-(5-chloro-1-ethylbenzimidazol-2-yl)-7-(3,4-dichlorophenyl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	449154: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0570	uM
(3S,4R)-4-[butyl-(4-ethylphenyl)sulfonylamino]-3-hydroxy-2,2-dimethyl-N-(2-phenylethyl)-3,4-dihydrochromene-6-carboxamide	290686: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0570	uM
(7R)-6-(2-cyclohexyl-1,2,4-triazol-3-yl)-7-(3,4-dichlorophenyl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	730777: Antagonist activity at human Kv1.5 expressed in mouse L929 cells assessed as inhibition of delayed rectifier repolarization current by patch clamp assay	ic50	0.0590	uM
3-cyano-N-(2-hydroxyethyl)-6-methoxy-4-phenylisoquinoline-1-carboxamide	272574: Antagonist activity at human Kv1.5 channel expressed in CHO cell membrane by HT clamp assay	ic50	0.0600	uM
N-[4-[[(4-methoxy-1,1-dioxo-1,2-benzothiazol-3-ylidene)amino]methyl]-4-phenylcyclohexyl]ethanesulfonamide	1249323: Inhibition of human KV1.5 expressed in mouse L929 cells assessed as decrease in ultrarapid potassium current amplitude	ic50	0.0600	uM
(2S)-3-[[(1S,2S)-2-(dipropylamino)-1,2-dipyridin-2-ylethyl]-propylamino]propane-1,2-diol	1594159: Inhibition of Kv1.5 in human atrial myocytes assessed as blockade of Ikur current	ic50	0.0600	uM
N-[(3S,4R)-6-[(2S)-2-[(2,6-dimethylanilino)methyl]pyrrolidine-1-carbonyl]-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-4-ethylbenzenesulfonamide	329660: Inhibition of human Kv1.5 channel expressed in mouse L929 cells assessed as blockade of ultra rapidly activating potassium current by voltage clamp technique	ic50	0.0600	uM
5-phenyl-2-pyridin-3-yl-N-(pyridin-2-ylmethyl)quinazolin-4-amine	1447683: Inhibition of recombinant human Kv1.5 expressed in mouse L929 cells by patch clamp assay	ic50	0.0600	uM
6-[2-[2-(3,5-dichlorophenyl)-3-pyridinyl]-1-pyridin-3-ylethyl]pyridin-2-amine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0620	uM
7-(3,4-dichlorophenyl)-6-(4-fluoro-1-methylbenzimidazol-2-yl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine	449154: Inhibition of human Kv1.5 channel expressed in mouse L929 cells	ic50	0.0640	uM
3-[2-(2,2-dipyridin-3-ylethyl)phenyl]-N,N-dimethylbenzamide	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0640	uM
3-[2-(2,2-dipyridin-3-ylethyl)phenyl]pyridine	1437176: Inhibition of Kv1.5 (unknown origin)	ic50	0.0640	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
vernakalant	affects binding, decreases activity	2
Cisplatin	increases response to substance, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
Terfenadine	decreases activity	2
terbufos	increases methylation	1
trichostatin A	decreases expression	1
diallyl trisulfide	decreases activity	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
ebastine	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acrolein	increases expression, decreases reaction	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases response to substance	1
Fonofos	increases methylation	1
Eugenol	decreases activity	1
Fluorouracil	increases response to substance	1
Ketoconazole	decreases activity	1
Parathion	increases methylation	1
Pergolide	decreases activity	1
Potassium	increases transport	1
Progesterone	decreases activity	1
Rotenone	decreases reaction, increases expression	1
Tamoxifen	decreases expression	1
Valproic Acid	affects expression	1

ChEMBL screening assays

152 unique, capped per target: 130 binding, 14 functional, 5 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1787442	Binding	Inhibition of human recombinant Kv channel at 10 uM by radioligand binding assay	Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. — Bioorg Med Chem Lett
CHEMBL5522525	Toxicity	Inhibition of human K+ channel by automated electrophysiology	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem
CHEMBL4039283	ADMET	Inhibition of human Kv1.5 expressed in CHO cells by automated patch clamp assay	Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation. — J Med Chem

Cellosaurus cell lines

10 cell lines: 6 transformed cell line, 2 spontaneously immortalized cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C0Y1	B’SYS CHO Kv1.5	Spontaneously immortalized cell line	Female
CVCL_E5JI	HEK293 Kv1.5	Transformed cell line	Female
CVCL_E5JJ	HEK293 Kv1.5-12PA	Transformed cell line	Female
CVCL_E5JK	HEK293 Kv1.5-DeltaN209	Transformed cell line	Female
CVCL_E5JL	HEK293 Kv1.5-DeltaPro	Transformed cell line	Female
CVCL_E5JM	HEK293 Kv1.5-Kv1.4NT	Transformed cell line	Female
CVCL_H517	HEK293/hKv1.5	Transformed cell line	Female
CVCL_LC65	PrecisION hKv1.5-CHO	Spontaneously immortalized cell line	Female
CVCL_QX79	UNIBSi001-A	Induced pluripotent stem cell	Male
CVCL_ZB29	ZZUSAHi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04931693	PHASE4	COMPLETED	PECs Block for Pacemaker Insertion in Children
NCT05666219	PHASE4	WITHDRAWN	Reversal of Complete Heart Block With Aminophylline in Inferior Wall Myocardial Infarction Patients
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.