KCNS3

Summary

KCNS3 (potassium voltage-gated channel modifier subfamily S member 3, HGNC:6302) is a protein-coding gene on chromosome 2p24.2, encoding Delayed-rectifier potassium channel regulatory subunit KCNS3 (Q9BQ31). Potassium channel regulatory subunit that modulates the delayed rectifier potassium channel activity of KCNB1 by namely slowing down the deactivation and inactivation time constants.

Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 3790 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_002252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6302
Approved symbol	KCNS3
Name	potassium voltage-gated channel modifier subfamily S member 3
Location	2p24.2
Locus type	gene with protein product
Status	Approved
Aliases	Kv9.3
Ensembl gene	ENSG00000170745
Ensembl biotype	protein_coding
OMIM	603888
Entrez	3790

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 20 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000304101, ENST00000403915, ENST00000419802, ENST00000465292, ENST00000481414, ENST00000869571, ENST00000869572, ENST00000869573, ENST00000869574, ENST00000869575, ENST00000869576, ENST00000869577, ENST00000920631, ENST00000920632, ENST00000920633, ENST00000920634, ENST00000920635, ENST00000954193, ENST00000954194, ENST00000954195, ENST00000954196, ENST00000954197

RefSeq mRNA: 2 — MANE Select: NM_002252 NM_001282428, NM_002252

CCDS: CCDS1692

Canonical transcript exons

ENST00000304101 — 3 exons

Exon	Start	End
ENSE00001162610	17917680	17917871
ENSE00001166371	17930950	17932958
ENSE00001812111	17878667	17878806

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 93.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7489 / max 49.6315, expressed in 930 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19097	2.4407	891
19098	0.3082	159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	93.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.43	gold quality
visceral pleura	UBERON:0002401	93.26	gold quality
quadriceps femoris	UBERON:0001377	92.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.86	gold quality
biceps brachii	UBERON:0001507	91.11	gold quality
pigmented layer of retina	UBERON:0001782	90.75	gold quality
skeletal muscle tissue	UBERON:0001134	90.59	gold quality
hair follicle	UBERON:0002073	90.45	silver quality
skeletal muscle organ	UBERON:0014892	89.74	gold quality
muscle organ	UBERON:0001630	89.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.12	gold quality
palpebral conjunctiva	UBERON:0001812	89.00	gold quality
muscle of leg	UBERON:0001383	88.95	gold quality
gastrocnemius	UBERON:0001388	88.29	gold quality
diaphragm	UBERON:0001103	88.14	silver quality
upper lobe of left lung	UBERON:0008952	87.78	gold quality
upper lobe of lung	UBERON:0008948	87.72	gold quality
lung	UBERON:0002048	87.43	gold quality
pancreatic ductal cell	CL:0002079	86.76	gold quality
muscle tissue	UBERON:0002385	86.61	gold quality
right lung	UBERON:0002167	86.47	gold quality
triceps brachii	UBERON:0001509	86.39	gold quality
secondary oocyte	CL:0000655	85.92	gold quality
lower lobe of lung	UBERON:0008949	85.38	gold quality
deltoid	UBERON:0001476	84.33	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.68	gold quality
gluteal muscle	UBERON:0002000	83.06	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	82.90	gold quality
calcaneal tendon	UBERON:0003701	82.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.98
E-GEOD-36552	no	86.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting KCNS3, 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-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4251	99.40	69.19	3363

Literature-anchored findings (GeneRIF, showing 7)

• Our findings suggest that SNPs located at the 3’ downstream region of KCNS3 have a significant role in the etiology of AHR. (PMID:15714333)
• formation of heteromeric Kv2.1/Kv9.3 channels of fixed stoichiometry consisting of three Kv2.1 subunits and one Kv9.3 subunit (PMID:15827117)
• There is evidence of heteromultimeric Kv2.1/Kv9.3 channel expression in control of middle cerebral arterial diameter. (PMID:20876197)
• stromatoxin-1 -sensitive KV2-containing channels are expressed in detrusor smooth muscle (DSM); they control DSM excitability, intracellular Ca2+ levels, and myogenic and nerve-evoked contractions (PMID:22422395)
• study concluded that potassium voltage-gated channel K(V)9.3 is localised to human placental vascular tissues and syncytiotrophoblast (PMID:22943705)
• By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects than in controls. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower. (PMID:24170294)
• Association analysis and polygenic risk score evaluation of 38 GWAS-identified Loci in a Chinese population with Parkinson’s disease. (PMID:34352340)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcns3a	ENSDARG00000006891
danio_rerio	kcns3b	ENSDARG00000029511
mus_musculus	Kcns3	ENSMUSG00000043673
rattus_norvegicus	Kcns3	ENSRNOG00000004899

Paralogs (31): KCNG1 (ENSG00000026559), 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), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Delayed-rectifier potassium channel regulatory subunit KCNS3 — Q9BQ31 (reviewed: Q9BQ31)

Alternative names: Delayed-rectifier K(+) channel alpha subunit 3, Delayed-rectifier potassium channel subunit Kv9.3, Potassium voltage-gated channel subfamily S member 3

All UniProt accessions (2): Q9BQ31, C9J187

UniProt curated annotations — full annotation on UniProt →

Function. Potassium channel regulatory subunit that modulates the delayed rectifier potassium channel activity of KCNB1 by namely slowing down the deactivation and inactivation time constants. While it does not form functional channel on its own, it can form functional heterotetrameric channels with KCNB1.

Subunit / interactions. Heterotetramer with KCNB1. Does not form homomultimers.

Subcellular location. Cell membrane.

Tissue specificity. Detected in whole normal term placental and placental chorionic plate arteries and veins. Detected in syncytiotrophoblast and in blood vessel endothelium within intermediate villi and chorionic plate (at protein level). Detected in most tissues, but not in peripheral blood lymphocytes. The highest levels of expression are in lung.

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. S (TC 1.A.1.2) subfamily. Kv9.3/KCNS3 sub-subfamily.

RefSeq proteins (2): NP_001269357, NP_002243* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003971	K_chnl_volt-dep_Kv5/Kv9	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 (21 total): topological domain 8, transmembrane region 6, intramembrane region 2, sequence variant 2, chain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ31-F1	78.78	0.39

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-422356	Regulation of insulin secretion

MSigDB gene sets: 170 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_POTASSIUM_ION_TRANSPORT, MULLIGHAN_NPM1_SIGNATURE_3_UP, BENPORATH_ES_WITH_H3K27ME3, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, CAATGCA_MIR33, GGGNNTTTCC_NFKB_Q6_01, AACTTT_UNKNOWN, GOBP_PROTEIN_HOMOOLIGOMERIZATION, WHN_B

GO Biological Process (8): 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), transmembrane transport (GO:0055085)

GO Molecular Function (6): delayed rectifier potassium channel activity (GO:0005251), potassium channel regulator activity (GO:0015459), 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 (7): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), cytoplasm (GO:0005737), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Potassium Channels	1
Regulation of insulin secretion	1
Neuronal System	1
Metabolism	1
Integration of energy metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transport	2
potassium channel activity	2
cytoplasm	2
regulation of membrane potential	1
metal ion transport	1
protein complex oligomerization	1
potassium ion transport	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
cellular process	1
voltage-gated potassium channel activity	1
ion channel regulator activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
voltage-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
intracellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1831 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNS3	KCNB1	Q14721	950
KCNS3	KCNA2	P16389	646
KCNS3	KCNAB1	Q14722	567
KCNS3	KCNMB1	P78475	560
KCNS3	PLA2G7	Q13093	549
KCNS3	SCGB2A1	O75556	548
KCNS3	SCGB3A2	Q96PL1	547
KCNS3	MUC7	Q8TAX7	547
KCNS3	HNMT	P50135	541
KCNS3	PHF11	Q9UIL8	499
KCNS3	PTGDR2	Q9Y5Y4	497
KCNS3	ADAM33	Q9BZ11	497
KCNS3	KCNA5	P22460	483
KCNS3	KCND3	Q9UK17	455
KCNS3	KCNAB3	O43448	438

IntAct

4 interactions, top by confidence:

A	B	Type	Score
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	KCNS3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (66): SUCO (Affinity Capture-MS), TAPT1 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), TAOK2 (Affinity Capture-MS), C2CD2L (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), KCNB2 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), REEP4 (Affinity Capture-MS), FIGNL1 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), RHBDF2 (Affinity Capture-MS), ANKRD13C (Affinity Capture-MS), ST7L (Affinity Capture-MS)

ESM2 similar proteins: A0A072VMJ3, F4IME1, F4IME2, G7IBJ4, G7JND3, O35174, O48538, O81209, O81210, O81211, O82226, O88759, Q5ZAJ0, Q6J2K5, Q6R8G2, Q6R8G3, Q6R8G6, Q84M97, Q8BQZ8, Q8GWD2, Q8L7Z0, Q8RWS9, Q948U0, Q9BQ31, Q9ER26, Q9FIJ0, Q9FJD6, Q9FXH6, Q9LD37, Q9LD40, Q9LDR2, Q9LEQ3, Q9LH74, Q9LNJ0, Q9LPG3, Q9LYG9, Q9LZU9, Q9M0A4, Q9S9N5, Q9SBI0

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

1 interactions.

A	Effect	B	Mechanism
KCNS3	“down-regulates quantity”	potassium(1+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

930 predictions. Top by Δscore:

Variant	Effect	Δscore
2:17917870:GG:G	donor_gain	1.0000
2:17917871:GG:G	donor_gain	1.0000
2:17917872:G:GG	donor_gain	0.9900
2:17917872:GTAAG:G	donor_loss	0.9900
2:17917873:T:A	donor_loss	0.9900
2:17930945:TCCA:T	acceptor_loss	0.9900
2:17930946:CCA:C	acceptor_loss	0.9900
2:17930947:CA:C	acceptor_loss	0.9900
2:17930948:A:AC	acceptor_loss	0.9900
2:17930948:A:AG	acceptor_gain	0.9900
2:17930949:G:A	acceptor_loss	0.9900
2:17930949:G:GG	acceptor_gain	0.9900
2:17917676:GCA:G	acceptor_loss	0.9800
2:17917677:CA:C	acceptor_loss	0.9800
2:17917678:A:AC	acceptor_loss	0.9800
2:17917679:G:GT	acceptor_loss	0.9800
2:17917679:GGT:G	acceptor_gain	0.9700
2:17917679:GGTGA:G	acceptor_gain	0.9700
2:17930949:GGT:G	acceptor_gain	0.9700
2:17878044:TCGG:T	donor_loss	0.9600
2:17878046:GGTGA:G	donor_loss	0.9600
2:17878047:G:GG	donor_gain	0.9600
2:17878047:GTG:G	donor_loss	0.9600
2:17878048:T:G	donor_loss	0.9600
2:17878049:GAGTG:G	donor_loss	0.9600
2:17878057:GAA:G	donor_gain	0.9600
2:17917747:T:TA	acceptor_gain	0.9600
2:17928737:A:T	donor_gain	0.9600
2:17930948:AG:A	acceptor_gain	0.9600
2:17930949:GG:G	acceptor_gain	0.9600

AlphaMissense

3275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:17931213:T:C	F69L	1.000
2:17931214:T:C	F69S	1.000
2:17931215:T:A	F69L	1.000
2:17931215:T:G	F69L	1.000
2:17931220:G:C	R71P	1.000
2:17931324:T:A	W106R	1.000
2:17931324:T:C	W106R	1.000
2:17931325:G:C	W106S	1.000
2:17931326:G:C	W106C	1.000
2:17931326:G:T	W106C	1.000
2:17932095:T:A	W363R	1.000
2:17932095:T:C	W363R	1.000
2:17932107:A:C	S367R	1.000
2:17932109:C:A	S367R	1.000
2:17932109:C:G	S367R	1.000
2:17932188:G:C	G394R	1.000
2:17932189:G:A	G394D	1.000
2:17931073:G:A	G22E	0.999
2:17931073:G:T	G22V	0.999
2:17931106:T:A	L33H	0.999
2:17931124:C:T	T39I	0.999
2:17931127:G:C	R40T	0.999
2:17931128:A:C	R40S	0.999
2:17931128:A:T	R40S	0.999
2:17931139:T:C	L44P	0.999
2:17931177:T:C	C57R	0.999
2:17931178:G:A	C57Y	0.999
2:17931179:T:G	C57W	0.999
2:17931181:A:T	D58V	0.999
2:17931214:T:G	F69C	0.999

dbSNP variants (sampled 300 via entrez): RS1000022910 (2:17911745 C>T), RS1000131503 (2:17904794 G>C), RS1000162714 (2:17905019 G>A), RS1000175900 (2:17884923 T>C), RS1000179919 (2:17929458 C>G,T), RS1000232322 (2:17929276 T>C), RS1000324188 (2:17890841 C>T), RS1000449155 (2:17897855 T>A), RS1000471359 (2:17909003 T>G), RS1000493037 (2:17905919 T>C,G), RS1000500609 (2:17911478 T>C), RS1000544824 (2:17886208 T>G), RS1000569842 (2:17930400 G>A,C), RS1000611542 (2:17884639 G>A), RS1000715722 (2:17899100 C>A,T)

Disease associations

OMIM: gene MIM:603888 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST002828_10	Urate levels in obese individuals	2.000000e-06
GCST004031_6	QT interval (sulfonylurea treatment interaction)	8.000000e-08
GCST004183_9	Lung function (FEV1)	7.000000e-08
GCST004185_51	Lung function (FEV1/FVC)	8.000000e-09
GCST005147_84	Colonoscopy-negative controls vs population controls	1.000000e-06
GCST005152_12	Colorectal cancer	3.000000e-06
GCST006274_2	Systolic blood pressure night-to-day ratio in hypertension	6.000000e-06
GCST007429_103	Lung function (FVC)	2.000000e-07
GCST007430_90	Peak expiratory flow	5.000000e-12
GCST007431_71	Lung function (FEV1/FVC)	4.000000e-40
GCST007432_112	FEV1	4.000000e-26
GCST008156_28	Hip circumference adjusted for BMI	5.000000e-07
GCST008163_439	Height	3.000000e-06
GCST008480_3	Lung function (FEV1)	3.000000e-11
GCST008481_3	Lung function (FEV1/FVC)	1.000000e-15
GCST008839_142	Height	6.000000e-10
GCST009325_86	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-08
GCST009531_4	Body fat percentage	4.000000e-12
GCST010059_6	Physiological traits	4.000000e-06
GCST011346_8	Total cholesterol levels	3.000000e-12
GCST011347_9	Low density lipoprotein cholesterol levels	1.000000e-16
GCST011584_4	Metastatic colorectal cancer survival in treatment with chemotherapy plus biologics	5.000000e-06
GCST011584_6	Metastatic colorectal cancer survival in treatment with chemotherapy plus biologics	8.000000e-06
GCST012490_234	Femur bone mineral density x serum urate levels interaction	5.000000e-10
GCST012490_35	Femur bone mineral density x serum urate levels interaction	4.000000e-12

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004682	QT interval
EFO:0007922	response to sulfonylurea
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0008460	colorectal health
EFO:0006944	systolic blood pressure change measurement
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0008039	BMI-adjusted hip circumference
EFO:0007800	body fat percentage
EFO:0005937	longitudinal BMI measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0000714	survival time
EFO:1001480	metastatic colorectal cancer

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	7
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Vorinostat	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
terbufos	decreases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	affects cotreatment, increases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression	1
lead chloride	affects cotreatment, increases expression	1
cadmium sulfate	increases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
bisphenol S	affects methylation	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Catechin	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

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2A8	HAP1 KCNS3 (-) 1	Cancer cell line	Male
CVCL_E2A9	HAP1 KCNS3 (-) 2	Cancer cell line	Male
CVCL_YA71	IDG-HEK293T-KCNS3-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder