KCNG1

Summary

KCNG1 (potassium voltage-gated channel modifier subfamily G member 1, HGNC:6248) is a protein-coding gene on chromosome 20q13.13, encoding Voltage-gated potassium channel regulatory subunit KCNG1 (Q9UIX4). Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1 or KCNB2, can modulate their expression and their gating kinetics by acting on deactivation upon repolarization and inactivation during maintained depolarization.

Voltage-gated potassium (Kv) 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. This gene encodes a member of the potassium channel, voltage-gated, subfamily G. This gene is abundantly expressed in skeletal muscle. Multiple alternatively spliced transcript variants have been found in normal and cancerous tissues.

Source: NCBI Gene 3755 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_002237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6248
Approved symbol	KCNG1
Name	potassium voltage-gated channel modifier subfamily G member 1
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	Kv6.1, kH2, K13
Ensembl gene	ENSG00000026559
Ensembl biotype	protein_coding
OMIM	603788
Entrez	3755

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 36 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371571, ENST00000424171, ENST00000433903, ENST00000439216, ENST00000447736, ENST00000506387, ENST00000854122, ENST00000939799, ENST00000939800, ENST00000939801, ENST00000939802, ENST00000939803, ENST00000939804, ENST00000939805, ENST00000939806, ENST00000939807, ENST00000939808, ENST00000939809, ENST00000939810, ENST00000939811, ENST00000939812, ENST00000939813, ENST00000939814, ENST00000939815, ENST00000939816, ENST00000939817, ENST00000939818, ENST00000939819, ENST00000939820, ENST00000939821, ENST00000939822, ENST00000939823, ENST00000939824, ENST00000939825, ENST00000953144, ENST00000953145, ENST00000953146

RefSeq mRNA: 1 — MANE Select: NM_002237 NM_002237

CCDS: CCDS13436

Canonical transcript exons

ENST00000371571 — 3 exons

Exon	Start	End
ENSE00001455524	51003656	51004806
ENSE00001673859	51022870	51023107
ENSE00003794610	51009565	51010364

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 90.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3793 / max 175.6550, expressed in 1227 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187909	9.2795	1225
187908	0.0998	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	90.82	gold quality
body of uterus	UBERON:0009853	87.82	gold quality
ventricular zone	UBERON:0003053	87.23	gold quality
left uterine tube	UBERON:0001303	86.77	gold quality
ganglionic eminence	UBERON:0004023	84.88	gold quality
stromal cell of endometrium	CL:0002255	84.73	gold quality
buccal mucosa cell	CL:0002336	83.59	silver quality
cauda epididymis	UBERON:0004360	83.34	gold quality
myometrium	UBERON:0001296	83.29	gold quality
cervix squamous epithelium	UBERON:0006922	81.46	gold quality
entorhinal cortex	UBERON:0002728	80.67	gold quality
seminal vesicle	UBERON:0000998	79.47	gold quality
cingulate cortex	UBERON:0003027	79.33	gold quality
anterior cingulate cortex	UBERON:0009835	79.09	gold quality
temporal lobe	UBERON:0001871	78.46	gold quality
right frontal lobe	UBERON:0002810	78.42	gold quality
amygdala	UBERON:0001876	78.33	gold quality
prefrontal cortex	UBERON:0000451	78.14	gold quality
uterus	UBERON:0000995	77.75	gold quality
embryo	UBERON:0000922	77.47	gold quality
neocortex	UBERON:0001950	77.17	gold quality
cranial nerve II	UBERON:0000941	77.08	gold quality
pancreatic ductal cell	CL:0002079	76.82	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	76.62	gold quality
frontal cortex	UBERON:0001870	76.61	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.39	gold quality
granulocyte	CL:0000094	76.30	gold quality
cerebral cortex	UBERON:0000956	76.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.69
E-HCAD-30	no	45.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting KCNG1, 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-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-1288-3P	96.86	66.95	536
HSA-MIR-3181	88.42	63.57	25

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcng1	ENSDARG00000099038
mus_musculus	Kcng1	ENSMUSG00000074575
rattus_norvegicus	Kcng1	ENSRNOG00000054314

Paralogs (31): KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), 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

Voltage-gated potassium channel regulatory subunit KCNG1 — Q9UIX4 (reviewed: Q9UIX4)

Alternative names: Potassium voltage-gated channel subfamily G member 1, Voltage-gated potassium channel subunit Kv6.1, kH2

All UniProt accessions (5): A0A075B6P6, A2A2I8, A2A2I9, Q9UIX4, Q5JXL4

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1 or KCNB2, can modulate their expression and their gating kinetics by acting on deactivation upon repolarization and inactivation during maintained depolarization. Potassium channel subunit that does not form functional channels by itself.

Subunit / interactions. Heterotetramer with KCNB1. Heterotetramer with KCNB2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in brain and placenta, and at much lower levels in kidney and pancreas.

Domain organisation. 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. G (TC 1.A.1.2) subfamily. Kv6.1/KCNG1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UIX4-1	1	yes
Q9UIX4-2	2

RefSeq proteins (1): NP_002228* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003969	K_chnl_volt-dep_Kv6	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

UniProt features (25 total): topological domain 8, transmembrane region 6, intramembrane region 2, splice variant 2, sequence conflict 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIX4-F1	79.76	0.35

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: 111 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, HAMAI_APOPTOSIS_VIA_TRAIL_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_POTASSIUM_ION_TRANSPORT, GOBP_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, DACOSTA_ERCC3_ALLELE_XPCS_VS_TTD_UP, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL

GO Biological Process (9): action potential (GO:0001508), potassium ion transport (GO:0006813), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), regulation of potassium ion transmembrane transport (GO:1901379), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), regulation of potassium ion transport (GO:0043266), transmembrane transport (GO:0055085)

GO Molecular Function (5): voltage-gated potassium channel activity (GO:0005249), potassium channel regulator activity (GO:0015459), monoatomic ion channel activity (GO:0005216), 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
potassium ion transport	2
transport	2
potassium channel activity	2
regulation of membrane potential	1
metal ion transport	1
protein complex oligomerization	1
monoatomic cation transmembrane transport	1
regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
regulation of metal ion transport	1
cellular process	1
voltage-gated monoatomic cation channel activity	1
ion channel regulator activity	1
monoatomic ion transmembrane transporter activity	1
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

1656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNG1	HNRNPK	P61978	882
KCNG1	FMR1	Q06787	877
KCNG1	FXR2	P51116	873
KCNG1	PCBP2	Q15366	840
KCNG1	FXR1	P51114	831
KCNG1	PCBP1	Q15365	820
KCNG1	GGCX	P38435	701
KCNG1	NOVA2	Q9UNW9	617
KCNG1	VKORC1	Q9BQB6	582
KCNG1	NUFIP2	Q7Z417	578
KCNG1	NUFIP1	Q9UHK0	575
KCNG1	CYFIP1	Q7L576	551
KCNG1	HNRNPDL	O14979	536
KCNG1	KCNK13	Q9HB14	526
KCNG1	KCNK6	Q9Y257	508

IntAct

18 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
KCNG1	PYCR3	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	KCNG1	psi-mi:“MI:0915”(physical association)	0.400
	ABCD4	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
TLR9	ABCD4	psi-mi:“MI:0914”(association)	0.350
DCST1	ADCY3	psi-mi:“MI:0914”(association)	0.350
TMED7	ATP9A	psi-mi:“MI:0914”(association)	0.350
KCNG1	UBB	psi-mi:“MI:0914”(association)	0.350
CCDC107	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Proximity Label-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-RNA), KCNB2 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), UBB (Affinity Capture-MS), KCNG1 (Affinity Capture-MS), KCNG1 (Affinity Capture-MS)

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 24 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	6	11.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

614 predictions. Top by Δscore:

Variant	Effect	Δscore
20:51010363:GCC:G	acceptor_loss	1.0000
20:51010365:C:CC	acceptor_gain	1.0000
20:51004805:CC:C	acceptor_gain	0.9900
20:51004806:CC:C	acceptor_gain	0.9900
20:51004807:C:CG	acceptor_loss	0.9900
20:51004808:T:C	acceptor_loss	0.9900
20:51009559:TCTTA:T	donor_loss	0.9900
20:51009560:CTTA:C	donor_loss	0.9900
20:51009561:TTAC:T	donor_loss	0.9900
20:51009562:TACCT:T	donor_loss	0.9900
20:51009564:C:CA	donor_loss	0.9900
20:51009564:CCTG:C	donor_gain	0.9900
20:51010360:CGGGC:C	acceptor_gain	0.9900
20:51010362:GGC:G	acceptor_gain	0.9900
20:51010363:GC:G	acceptor_gain	0.9900
20:51010364:CC:C	acceptor_gain	0.9900
20:51013420:A:C	donor_gain	0.9900
20:51022519:T:A	donor_gain	0.9900
20:51004803:GGCC:G	acceptor_gain	0.9800
20:51004807:C:T	acceptor_gain	0.9800
20:51009563:A:AC	donor_gain	0.9800
20:51009564:C:CC	donor_gain	0.9800
20:51010361:GGGC:G	acceptor_gain	0.9800
20:51013419:A:AC	donor_gain	0.9800
20:51022523:T:TA	donor_gain	0.9800
20:51004802:TGGCC:T	acceptor_gain	0.9700
20:51004803:GGCCC:G	acceptor_gain	0.9700
20:51004804:GCCCT:G	acceptor_gain	0.9700
20:51004807:C:CC	acceptor_gain	0.9700
20:51010367:G:C	acceptor_gain	0.9700

AlphaMissense

3338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:51004192:G:C	F463L	1.000
20:51004192:G:T	F463L	1.000
20:51004194:A:G	F463L	1.000
20:51004217:G:T	P455Q	1.000
20:51004238:C:T	G448D	1.000
20:51004239:C:G	G448R	1.000
20:51004240:G:C	S447R	1.000
20:51004240:G:T	S447R	1.000
20:51004242:T:G	S447R	1.000
20:51004744:G:C	F279L	1.000
20:51004744:G:T	F279L	1.000
20:51004746:A:G	F279L	1.000
20:51009877:C:A	W154C	1.000
20:51009877:C:G	W154C	1.000
20:51009879:A:G	W154R	1.000
20:51009879:A:T	W154R	1.000
20:51009989:A:G	F117S	1.000
20:51009991:G:C	F116L	1.000
20:51009991:G:T	F116L	1.000
20:51009993:A:G	F116L	1.000
20:51004193:A:G	F463S	0.999
20:51004201:G:C	F460L	0.999
20:51004201:G:T	F460L	0.999
20:51004203:A:G	F460L	0.999
20:51004217:G:C	P455R	0.999
20:51004229:A:T	L451H	0.999
20:51004232:A:G	L450P	0.999
20:51004249:G:C	S444R	0.999
20:51004249:G:T	S444R	0.999
20:51004251:T:G	S444R	0.999

dbSNP variants (sampled 300 via entrez): RS1000022586 (20:51020640 C>A), RS1000025280 (20:51008328 T>A), RS1000057784 (20:51008493 C>T), RS1000124957 (20:51023560 C>A,T), RS1000234865 (20:51017845 T>C), RS1000314264 (20:51011520 T>C), RS1000648646 (20:51013097 A>C), RS1000688609 (20:51018160 C>T), RS1000886463 (20:51006811 C>T), RS1001301470 (20:51023117 G>A,T), RS1001316061 (20:51009941 G>A,T), RS1001370040 (20:51015166 G>A), RS1001558662 (20:51003390 G>A,C,T), RS1001648006 (20:51016540 C>T), RS1001974276 (20:51013800 A>T)

Disease associations

OMIM: gene MIM:603788 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002114_4	Molar-incisor hypomineralization	5.000000e-06
GCST003082_4	Longitudinal change in brain amyloid plaque burden	7.000000e-07
GCST006409_28	Allergic rhinitis	5.000000e-08
GCST008103_111	Bipolar disorder	4.000000e-06
GCST008115_15	Bipolar I disorder	6.000000e-08
GCST009372_2	Bipolar disorder or type 2 diabetes	4.000000e-08
GCST011767_4	Bipolar disorder	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005321	molar-incisor hypomineralization
EFO:0007646	amyloid plaque accumulation rate
EFO:0009963	bipolar I disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362996 (PROTEIN FAMILY)

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)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 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

PubChem BioAssay actives

2 with measured affinity, of 34 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Progesterone	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
methylmercuric chloride	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC668394	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Ethanol	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 20 binding, 1 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

Clinical trials (associated diseases)

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