KCNA7

Summary

KCNA7 (potassium voltage-gated channel subfamily A member 7, HGNC:6226) is a protein-coding gene on chromosome 19q13.33, encoding Potassium voltage-gated channel subfamily A member 7 (Q96RP8). Mediates the voltage-dependent potassium ion permeability of excitable membranes.

Potassium channels represent the most complex class of voltage-gated ion 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. The gene is expressed preferentially in skeletal muscle, heart and kidney. It is a candidate gene for inherited cardiac disorders.

Source: NCBI Gene 3743 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 91 total
• Druggable target: yes
• MANE Select transcript: NM_031886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6226
Approved symbol	KCNA7
Name	potassium voltage-gated channel subfamily A member 7
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	Kv1.7, HAK6
Ensembl gene	ENSG00000104848
Ensembl biotype	protein_coding
OMIM	176268
Entrez	3743

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000221444

RefSeq mRNA: 1 — MANE Select: NM_031886 NM_031886

CCDS: CCDS12755

Canonical transcript exons

ENST00000221444 — 2 exons

Exon	Start	End
ENSE00001129565	49072031	49072699
ENSE00001194038	49067397	49070878

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 92.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0197 / max 7.0937, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181986	0.0197	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.06	gold quality
vastus lateralis	UBERON:0001379	90.62	silver quality
hindlimb stylopod muscle	UBERON:0004252	89.95	gold quality
quadriceps femoris	UBERON:0001377	89.55	silver quality
skeletal muscle tissue	UBERON:0001134	88.11	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.67	silver quality
biceps brachii	UBERON:0001507	87.50	silver quality
gastrocnemius	UBERON:0001388	86.79	gold quality
muscle of leg	UBERON:0001383	86.07	gold quality
deltoid	UBERON:0001476	81.59	silver quality
muscle tissue	UBERON:0002385	80.39	gold quality
tibialis anterior	UBERON:0001385	77.61	silver quality
tendon of biceps brachii	UBERON:0008188	60.80	gold quality
endothelial cell	CL:0000115	60.20	gold quality
body of tongue	UBERON:0011876	59.83	silver quality
left ventricle myocardium	UBERON:0006566	59.42	gold quality
apex of heart	UBERON:0002098	58.42	gold quality
right atrium auricular region	UBERON:0006631	56.50	gold quality
myocardium	UBERON:0002349	56.29	gold quality
cardiac atrium	UBERON:0002081	56.15	gold quality
pancreatic ductal cell	CL:0002079	55.41	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
epithelial cell of pancreas	CL:0000083	54.09	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
tongue	UBERON:0001723	52.36	silver quality
heart left ventricle	UBERON:0002084	51.82	gold quality
cardiac ventricle	UBERON:0002082	51.65	gold quality
heart right ventricle	UBERON:0002080	50.23	gold quality
jejunum	UBERON:0002115	49.90	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting KCNA7, 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-1229-3P	99.97	66.49	906
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-6867-3P	98.12	66.07	1305

Literature-anchored findings (GeneRIF, showing 3)

• Expressed in heart, but not the cause of progressive familial heart block I. (PMID:11896454)
• The authors conclude that K(v) 1.7 contributes to the membrane-repolarizing current of beta cells during glucose-stimulated insulin. (PMID:22438204)
• For FOXK1 and KCNA7, the age effect on the sperm epigenome was replicated in an independent cohort of 188 sperm samples. (PMID:28171595)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcna7	ENSMUSG00000038201
rattus_norvegicus	Kcna7	ENSRNOG00000020779

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), 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 7 — Q96RP8 (reviewed: Q96RP8)

Alternative names: Voltage-gated potassium channel subunit Kv1.7

All UniProt accessions (1): Q96RP8

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.

Subunit / interactions. Heterotetramer of potassium channel proteins.

Subcellular location. Membrane.

Tissue specificity. Highly expressed in skeletal muscle, heart and kidney.

Domain organisation. The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Similarity. Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.7/KCNA7 sub-subfamily.

RefSeq proteins (1): NP_114092* (*=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
IPR005821	Ion_trans_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family
IPR048219	KCNA7_BTB_POZ	Domain

Pfam: PF00520, PF02214

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (14 total): transmembrane region 6, sequence variant 2, sequence conflict 2, chain 1, short sequence motif 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RP8-F1	82.12	0.61

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 (1): 231

Glycosylation sites (1): 191

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels

MSigDB gene sets: 75 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_HOMOOLIGOMERIZATION, MEF2_Q6_01, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_CATION_CHANNEL_COMPLEX, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_PLASMA_MEMBRANE_PROTEIN_COMPLEX, GOMF_VOLTAGE_GATED_MONOATOMIC_CATION_CHANNEL_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (7): action potential (GO:0001508), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (5): delayed rectifier potassium channel activity (GO:0005251), monoatomic ion channel activity (GO:0005216), voltage-gated potassium channel activity (GO:0005249), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
regulation of membrane potential	1
protein complex oligomerization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
voltage-gated potassium channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNA7	TRPM4	Q8TD43	825
KCNA7	SCN1B	Q07699	709
KCNA7	SCN4A	P35499	675
KCNA7	CACNG1	Q06432	579
KCNA7	SCN3A	Q9NY46	573
KCNA7	SCN5A	Q14524	571
KCNA7	SCN2A	Q99250	499
KCNA7	SCN1A	P35498	464
KCNA7	SCN3B	Q9NY72	451
KCNA7	KCNN4	O15554	448
KCNA7	KCNC3	Q14003	440
KCNA7	SHPK	Q9UHJ6	432
KCNA7	GRIN2A	Q12879	419
KCNA7	FSHB	P01225	417
KCNA7	KCNJ12	Q14500	410

IntAct

126 interactions, top by confidence:

A	B	Type	Score
ARHGEF12	KCNA7	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
SYNJ2BP	KCNA7	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA7	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440

ESM2 similar proteins: A2BDX4, A4K2T1, A4K2Y2, D4AD53, O15554, O73606, O88454, O89109, P15388, P17971, P17972, P35739, P48547, P59053, P59994, P59995, P97557, Q03719, Q0P583, Q17ST2, Q52PG9, Q5RC10, Q60565, Q63881, Q6IVV8, Q6PIU1, Q7TN37, Q80XM3, Q8BZN2, Q8CFS6, Q8HYZ1, Q8IV77, Q8R1P5, Q8R523, Q8TAE7, Q8TD43, Q8TDN1, Q8TDN2, Q96RP8, Q9ERS0

Diamond homologs: A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, G5EFC3, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16390, P17970, P17971, P17972, P22001, P22459, P22739, P25122, P48547, P59053, P59994, P59995

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Ras activation upon Ca2+ influx through NMDA receptor	5	53.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	47.9×	1e-12
Dopamine Neurotransmitter Release Cycle	5	46.8×	2e-06
Long-term potentiation	5	44.9×	2e-06
Neurexins and neuroligins	10	37.1×	1e-11
Protein-protein interactions at synapses	6	30.1×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	82.0×	2e-16
receptor clustering	7	56.0×	7e-09
protein localization to synapse	5	49.1×	4e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	3e-08
cell-cell adhesion	9	11.7×	4e-06
protein-containing complex assembly	8	11.7×	2e-05
regulation of small GTPase mediated signal transduction	5	9.2×	4e-03
chemical synaptic transmission	7	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

123 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49070875:GGAA:G	acceptor_gain	1.0000
19:49070879:C:CC	acceptor_gain	1.0000
19:49070874:GGGAA:G	acceptor_gain	0.9900
19:49070876:GAA:G	acceptor_gain	0.9900
19:49070877:AA:A	acceptor_gain	0.9900
19:49070878:ACT:A	acceptor_loss	0.9900
19:49070880:T:G	acceptor_loss	0.9900
19:49072029:A:AC	donor_gain	0.9900
19:49072029:A:C	donor_loss	0.9900
19:49072030:C:CC	donor_gain	0.9900
19:49072030:C:CG	donor_loss	0.9900
19:49072030:CCGGG:C	donor_gain	0.9900
19:49070882:C:CT	acceptor_gain	0.9700
19:49070766:T:TG	acceptor_gain	0.9500
19:49070883:A:T	acceptor_gain	0.9400
19:49072030:CCG:C	donor_gain	0.9300
19:49072029:AC:A	donor_gain	0.9200
19:49072030:CC:C	donor_gain	0.9200
19:49070767:C:G	acceptor_gain	0.9100
19:49072030:CCGG:C	donor_gain	0.8600
19:49072027:T:A	donor_gain	0.8200
19:49072306:C:CT	donor_gain	0.8000
19:49070878:ACTGC:A	acceptor_gain	0.7900
19:49070879:CTGC:C	acceptor_gain	0.7700
19:49070880:T:A	acceptor_gain	0.7300
19:49072064:G:A	donor_gain	0.7200
19:49072307:C:CT	donor_gain	0.7100
19:49070156:G:A	donor_gain	0.6600
19:49070801:C:CT	acceptor_gain	0.6500
19:49072314:T:TA	donor_gain	0.6500

AlphaMissense

2926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49070243:G:C	F397L	1.000
19:49070243:G:T	F397L	1.000
19:49070244:A:C	F397C	1.000
19:49070244:A:G	F397S	1.000
19:49070245:A:G	F397L	1.000
19:49070256:A:T	I393N	1.000
19:49070271:A:G	L388P	1.000
19:49070283:A:G	L384P	1.000
19:49070289:C:T	G382D	1.000
19:49070290:C:G	G382R	1.000
19:49070300:A:C	C378W	1.000
19:49070301:C:T	C378Y	1.000
19:49070310:C:T	G375D	1.000
19:49070349:C:A	G362V	1.000
19:49070349:C:T	G362E	1.000
19:49070383:A:G	W351R	1.000
19:49070383:A:T	W351R	1.000
19:49070450:G:C	S328R	1.000
19:49070450:G:T	S328R	1.000
19:49070452:T:G	S328R	1.000
19:49070564:C:A	K290N	1.000
19:49070564:C:G	K290N	1.000
19:49070774:G:C	F220L	1.000
19:49070774:G:T	F220L	1.000
19:49070776:A:G	F220L	1.000
19:49070245:A:T	F397I	0.999
19:49070251:A:G	S395P	0.999
19:49070253:A:T	V394D	0.999
19:49070256:A:C	I393S	0.999
19:49070259:A:T	V392D	0.999

dbSNP variants (sampled 300 via entrez): RS1000226270 (19:49073191 T>A), RS1000462682 (19:49068446 G>A), RS1000558742 (19:49071293 C>A,T), RS1002122626 (19:49071818 T>A), RS1003002220 (19:49071171 G>A,C), RS1003411955 (19:49070378 C>A,T), RS1003494116 (19:49071470 C>A), RS1003781427 (19:49069847 C>G,T), RS1004176861 (19:49073941 G>A), RS1004283500 (19:49067798 G>T), RS1004880069 (19:49073636 A>G), RS1005179224 (19:49071802 C>G,T), RS1005261077 (19:49072631 C>A,G), RS1005389996 (19:49067945 G>A), RS1005771939 (19:49067572 C>A)

Disease associations

OMIM: gene MIM:176268 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010796_2226	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-20
GCST010796_2227	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-17
GCST010796_2228	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2362996 (PROTEIN FAMILY), CHEMBL2773 (SINGLE PROTEIN)

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 (17 total), top 17:

Ligand	Action	Affinity	Parameter
ShK Toxin	Channel blocker	7.9	pIC50
noxiustoxin	Channel blocker	7.7	pIC50
margatoxin	Channel blocker	6.9	pIC50
conkunitzin-S1 toxin	Pore blocker	6.4	pIC50
flecainide	Channel blocker	5.1	pKd
CP-339818	Channel blocker	5.0	pIC50
nifedipine	Channel blocker	4.9	pIC50
quinidine	Channel blocker	4.8	pKd
verapamil	Channel blocker	4.8	pKd
resiniferatoxin	Channel blocker	4.7	pIC50
tedisamil	Channel blocker	4.7	pIC50
capsaicin	Channel blocker	4.6	pIC50
amiodarone	Channel blocker	4.5	pKd
diltiazem	Channel blocker	4.2	pIC50
tetraethylammonium	Channel blocker	4.1	pKd
fampridine	Channel blocker	3.6	pIC50
cromakalim	Channel blocker	3.3	pIC50

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 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
7.01	EC50	98	nM	CHEMBL444449

PubChem BioAssay actives

2 with measured affinity, of 40 total; 1 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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, increases expression, affects expression	2
dimethylselenide	decreases expression, increases expression, increases oxidation	1
perfluorooctane sulfonic acid	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects cotreatment, decreases expression	1
Reactive Oxygen Species	increases oxidation, decreases expression, increases expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

23 unique, capped per target: 21 binding, 1 toxicity, 1 admet

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
CHEMBL4407442	ADMET	Inhibition of Kv1.7 (unknown origin) at 3 uM relative to control	Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1JZ	PrecisION hKv1.7-CHO	Spontaneously immortalized cell line	Female
CVCL_YA58	IDG-HEK293T-KCNA7-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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