KCNH3

Summary

KCNH3 (potassium voltage-gated channel subfamily H member 3, HGNC:6252) is a protein-coding gene on chromosome 12q13.12, encoding Voltage-gated inwardly rectifying potassium channel KCNH3 (Q9ULD8). Pore-forming (alpha) subunit of a voltage-gated inwardly rectifying potassium channel.

The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23416 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 131 total
• Druggable target: yes
• MANE Select transcript: NM_012284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6252
Approved symbol	KCNH3
Name	potassium voltage-gated channel subfamily H member 3
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	Kv12.2, BEC1, elk2
Ensembl gene	ENSG00000135519
Ensembl biotype	protein_coding
OMIM	604527
Entrez	23416

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000257981, ENST00000548675, ENST00000550434, ENST00000551415, ENST00000649994, ENST00000965158

RefSeq mRNA: 2 — MANE Select: NM_012284 NM_001314030, NM_012284

CCDS: CCDS8786

Canonical transcript exons

ENST00000257981 — 15 exons

Exon	Start	End
ENSE00001161601	49556370	49556476
ENSE00001161607	49555620	49555951
ENSE00001161613	49554337	49554554
ENSE00001161622	49550080	49550329
ENSE00001161630	49549441	49549640
ENSE00001161638	49548895	49549173
ENSE00001161646	49544175	49544382
ENSE00001161686	49540899	49541132
ENSE00001161697	49557354	49558337
ENSE00001258589	49543915	49544072
ENSE00003507907	49557183	49557259
ENSE00003510540	49542706	49542839
ENSE00003578020	49541630	49541764
ENSE00003652709	49543275	49543518
ENSE00003846565	49539030	49539492

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 97.02.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2209 / max 93.8764, expressed in 414 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125338	2.0539	404
125340	0.0980	60
125339	0.0690	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	97.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.90	gold quality
anterior cingulate cortex	UBERON:0009835	95.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.65	gold quality
prefrontal cortex	UBERON:0000451	94.54	gold quality
amygdala	UBERON:0001876	94.28	gold quality
frontal cortex	UBERON:0001870	93.36	gold quality
frontal lobe	UBERON:0016525	93.36	gold quality
neocortex	UBERON:0001950	92.96	gold quality
caudate nucleus	UBERON:0001873	91.89	gold quality
cerebral cortex	UBERON:0000956	91.80	gold quality
putamen	UBERON:0001874	91.72	gold quality
right uterine tube	UBERON:0001302	91.42	gold quality
temporal lobe	UBERON:0001871	90.85	gold quality
nucleus accumbens	UBERON:0001882	90.29	gold quality
primary visual cortex	UBERON:0002436	89.82	gold quality
forebrain	UBERON:0001890	89.78	gold quality
Ammon’s horn	UBERON:0001954	89.63	gold quality
superior frontal gyrus	UBERON:0002661	88.58	gold quality
brain	UBERON:0000955	87.83	gold quality
pituitary gland	UBERON:0000007	87.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.61	gold quality
entorhinal cortex	UBERON:0002728	87.59	gold quality
postcentral gyrus	UBERON:0002581	87.08	gold quality
adenohypophysis	UBERON:0002196	86.58	gold quality
cerebellar hemisphere	UBERON:0002245	86.36	gold quality
cerebellar cortex	UBERON:0002129	86.09	gold quality
occipital lobe	UBERON:0002021	86.01	gold quality
kidney epithelium	UBERON:0004819	85.72	gold quality
parietal lobe	UBERON:0001872	85.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting KCNH3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-6877-5P	93.84	61.41	74

Literature-anchored findings (GeneRIF, showing 2)

• BEC1 is negatively involved in cognitive functions with no abnormal behaviors such as spontaneous seizures or motor dysfunction. (PMID:19923296)
• report on the binding of HIV-1 gp120 to the cytoplasmic C-terminus of the voltage-gated potassium channel BEC1, an interaction that can result in the repression of BEC’s activity and the inhibition of HIV-1 particle-release (PMID:20638388)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnh6a	ENSDARG00000001803
danio_rerio	kcnh6b	ENSDARG00000010296
danio_rerio	cngk	ENSDARG00000093267
mus_musculus	Kcnh3	ENSMUSG00000037579
rattus_norvegicus	Kcnh3	ENSRNOG00000057315
drosophila_melanogaster	sei	FBGN0003353
drosophila_melanogaster	Elk	FBGN0011589
drosophila_melanogaster	CG6026	FBGN0038676
drosophila_melanogaster	CngA	FBGN0261612
drosophila_melanogaster	Cngl	FBGN0263257
drosophila_melanogaster	Ih	FBGN0263397
drosophila_melanogaster	CngB	FBGN0266346
caenorhabditis_elegans		WBGENE00000487
caenorhabditis_elegans	tax-2	WBGENE00006525
caenorhabditis_elegans		WBGENE00006526
caenorhabditis_elegans		WBGENE00006830
caenorhabditis_elegans		WBGENE00022295

Paralogs (17): KCNH2 (ENSG00000055118), CNGB1 (ENSG00000070729), KCNH4 (ENSG00000089558), HCN2 (ENSG00000099822), CNGA4 (ENSG00000132259), HCN4 (ENSG00000138622), KCNH5 (ENSG00000140015), KCNH1 (ENSG00000143473), HCN3 (ENSG00000143630), CNGA3 (ENSG00000144191), HCN1 (ENSG00000164588), CNGB3 (ENSG00000170289), KCNH6 (ENSG00000173826), CNGA2 (ENSG00000183862), KCNH8 (ENSG00000183960), KCNH7 (ENSG00000184611), CNGA1 (ENSG00000198515)

Protein

Protein identifiers

Voltage-gated inwardly rectifying potassium channel KCNH3 — Q9ULD8 (reviewed: Q9ULD8)

Alternative names: Brain-specific eag-like channel 1, Ether-a-go-go-like potassium channel 2, Potassium voltage-gated channel subfamily H member 3, Voltage-gated potassium channel subunit Kv12.2

All UniProt accessions (2): A0A3B3ITH0, Q9ULD8

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming (alpha) subunit of a voltage-gated inwardly rectifying potassium channel. Charactherized by a fast rate of activation during depolarization followed by a rapid inactivation at much more depolarized value causing inward rectification due to a C-type inactivation mechanism. Exhibits a rapid recovery from inactivation.

Subunit / interactions. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Interacts with KCNE1 and KCNE3; these interactions regulate KCNH3 trafficking to the plasma membrane and its subsequent voltage-gated potassium channel activity.

Subcellular location. Cell membrane.

Tissue specificity. Detected only in brain, in particular in the telencephalon. Detected in the cerebral cortex, occipital pole, frontal and temporal lobe, putamen, amygdala, hippocampus and caudate nucleus.

Post-translational modifications. N-glycosylated. N-glycosylation mediates traffick to the cell membrane but is not necessary for voltage-gated potassium channel activity.

Similarity. Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.2/KCNH3 sub-subfamily.

RefSeq proteins (2): NP_001300959, NP_036416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR000595	cNMP-bd_dom	Domain
IPR000700	PAS-assoc_C	Domain
IPR001610	PAC	Repeat
IPR003938	K_chnl_volt-dep_EAG/ELK/ERG	Family
IPR003950	K_chnl_volt-dep_ELK	Family
IPR005821	Ion_trans_dom	Domain
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR035965	PAS-like_dom_sf	Homologous_superfamily
IPR050818	KCNH_animal-type	Family

Pfam: PF00027, PF00520, PF13426

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (30 total): topological domain 8, transmembrane region 6, region of interest 4, compositionally biased region 3, glycosylation site 3, domain 2, chain 1, intramembrane region 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULD8-F1	65.09	0.26

Functional residue map

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

Ligand- & substrate-binding residues (1): 582–697

Glycosylation sites (3): 421, 428, 436

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: 96 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, AREB6_01, GOBP_MONOATOMIC_CATION_TRANSPORT, TGCTGAY_UNKNOWN, TGANTCA_AP1_C, NRF2_Q4, P300_01, MODULE_95, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_TRANSPORTER_COMPLEX

GO Biological Process (6): potassium ion transport (GO:0006813), regulation of membrane potential (GO:0042391), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (5): inward rectifier potassium channel activity (GO:0005242), voltage-gated potassium channel activity (GO:0005249), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), 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
metal ion transport	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
potassium channel activity	1
voltage-gated monoatomic cation channel 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
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNH3	ELK1	P19419	768
KCNH3	TBC1D25	Q3MII6	684
KCNH3	CC2D1A	Q6P1N0	617
KCNH3	HOXD1	Q9GZZ0	607
KCNH3	KCNA2	P16389	605
KCNH3	KCNAB3	O43448	591
KCNH3	KCNA3	P22001	561
KCNH3	KCNF1	Q9H3M0	544
KCNH3	KCNQ3	O43525	540
KCNH3	KCNV1	Q6PIU1	500
KCNH3	KCNC4	Q03721	494
KCNH3	CACNB1	Q02641	493
KCNH3	SCN1A	P35498	490
KCNH3	KCNG1	Q9UIX4	488
KCNH3	KCNS2	Q9ULS6	487

IntAct

6 interactions, top by confidence:

A	B	Type	Score
KCNH3	env	psi-mi:“MI:0915”(physical association)	0.590
KCNH3	LRRC59	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (4): KCNH3 (Proximity Label-MS), KCNH3 (Positive Genetic), KCNH3 (Affinity Capture-RNA), KCNH4 (Negative Genetic)

ESM2 similar proteins: A2ARS0, A6NH11, A6QQ91, C9JTQ0, D3ZVB0, D4A929, G3MZC5, O75064, O95996, P16386, P46062, P58660, Q02011, Q08DF2, Q16619, Q29RK8, Q2TBW5, Q2VPB7, Q3TAP4, Q3U0S6, Q3U1Y4, Q562E7, Q5TA50, Q5U651, Q60753, Q63086, Q64375, Q68J42, Q6P9B9, Q6ZS72, Q86YV0, Q8BH02, Q8BQU6, Q8C2K5, Q8CHT3, Q8K0R6, Q8K2B0, Q8N9M5, Q8VD26, Q92791

Diamond homologs: A0A364LYQ6, A2XKR7, A6X554, B0G188, B8AX51, O34627, O48963, O49741, O49743, O64511, O65515, O82632, O89047, P58724, P69781, P93025, Q00858, Q01371, Q02280, Q10F25, Q1M667, Q2NB77, Q2NB98, Q2NCA3, Q2QYY8, Q2R2W1, Q2RBR1, Q48IV1, Q4ZSY3, Q54HA4, Q54KX0, Q54NM5, Q54TE3, Q54TM6, Q550D5, Q55C49, Q55GK0, Q59LY1, Q5HZ36, Q5Z8K3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2826 predictions. Top by Δscore:

Variant	Effect	Δscore
12:49539491:GC:G	donor_gain	1.0000
12:49539493:G:GG	donor_gain	1.0000
12:49541105:GC:G	donor_gain	1.0000
12:49541125:G:GT	donor_gain	1.0000
12:49541128:GAGCG:G	donor_gain	1.0000
12:49541130:GCG:G	donor_gain	1.0000
12:49541760:GACAG:G	donor_gain	1.0000
12:49541764:GGTA:G	donor_loss	1.0000
12:49541765:G:GC	donor_loss	1.0000
12:49542702:GCAGG:G	acceptor_loss	1.0000
12:49542703:CAGGT:C	acceptor_loss	1.0000
12:49542704:A:AG	acceptor_gain	1.0000
12:49542704:AG:A	acceptor_gain	1.0000
12:49542704:AGGT:A	acceptor_gain	1.0000
12:49542704:AGGTG:A	acceptor_gain	1.0000
12:49542705:G:GG	acceptor_gain	1.0000
12:49542705:GG:G	acceptor_gain	1.0000
12:49542705:GGT:G	acceptor_gain	1.0000
12:49542705:GGTG:G	acceptor_gain	1.0000
12:49542705:GGTGG:G	acceptor_gain	1.0000
12:49542821:C:T	donor_gain	1.0000
12:49542835:ATAAG:A	donor_loss	1.0000
12:49542837:AAGG:A	donor_loss	1.0000
12:49542839:GGTGG:G	donor_loss	1.0000
12:49542840:GTG:G	donor_loss	1.0000
12:49542841:T:A	donor_loss	1.0000
12:49543910:CACA:C	acceptor_loss	1.0000
12:49543911:ACAGA:A	acceptor_loss	1.0000
12:49543912:CAGAC:C	acceptor_loss	1.0000
12:49543913:A:AG	acceptor_gain	1.0000

AlphaMissense

6930 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:49539456:T:C	F14L	1.000
12:49539457:T:C	F14S	1.000
12:49539457:T:G	F14C	1.000
12:49539458:C:A	F14L	1.000
12:49539458:C:G	F14L	1.000
12:49539460:T:C	L15P	1.000
12:49539469:T:A	I18N	1.000
12:49539469:T:G	I18S	1.000
12:49539472:C:A	A19D	1.000
12:49539480:T:C	F22L	1.000
12:49539482:C:A	F22L	1.000
12:49539482:C:G	F22L	1.000
12:49540907:T:C	F29L	1.000
12:49540908:T:C	F29S	1.000
12:49540908:T:G	F29C	1.000
12:49540909:C:A	F29L	1.000
12:49540909:C:G	F29L	1.000
12:49540914:T:A	L31Q	1.000
12:49540914:T:C	L31P	1.000
12:49540917:G:A	G32D	1.000
12:49540950:T:A	V43D	1.000
12:49540952:T:C	Y44H	1.000
12:49540955:T:C	C45R	1.000
12:49540956:G:A	C45Y	1.000
12:49540957:C:G	C45W	1.000
12:49540959:C:A	S46Y	1.000
12:49540959:C:T	S46F	1.000
12:49540967:T:C	F49L	1.000
12:49540968:T:C	F49S	1.000
12:49540969:C:A	F49L	1.000

dbSNP variants (sampled 300 via entrez): RS1000072027 (12:49548407 G>A), RS1000163538 (12:49538008 C>T), RS1000458257 (12:49554987 C>A,T), RS1000470759 (12:49544015 G>A,C), RS1000522784 (12:49543619 G>A,C,T), RS1000566606 (12:49550814 C>T), RS1000940790 (12:49556767 T>C), RS1001070740 (12:49556454 C>A,G), RS1001139804 (12:49550325 C>T), RS1001464894 (12:49549891 T>C), RS1001470728 (12:49545485 T>C), RS1001492216 (12:49544366 C>G,T), RS1001710796 (12:49538725 G>T), RS1001957715 (12:49557766 A>C,G), RS1002064512 (12:49551594 A>G,T)

Disease associations

OMIM: gene MIM:604527 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005316_371	Intelligence (MTAG)	7.000000e-09
GCST90000050_52	Age at first birth	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009101	age at first birth measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2362996 (PROTEIN FAMILY), CHEMBL2363017 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
CX4	Inhibition	5.0	pIC50
Cs+	Pore blocker	1.2	pKd

ChEMBL bioactivities

71 potent at pChembl≥5 of 72 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
7.33	IC50	47	nM	CHEMBL3987187
7.28	IC50	52	nM	CHEMBL3902034
7.24	IC50	58	nM	CHEMBL3960526
7.19	IC50	65	nM	CHEMBL3908982
7.14	IC50	73	nM	CHEMBL3918973
7.11	IC50	77	nM	CHEMBL3979641
7.10	IC50	79	nM	CHEMBL3913727
7.08	IC50	84	nM	CHEMBL3916475
7.07	IC50	85	nM	CHEMBL3934480
7.07	IC50	85	nM	CHEMBL3912592
7.04	IC50	92	nM	CHEMBL3918716
7.00	IC50	100	nM	CHEMBL3941694
6.96	IC50	110	nM	CHEMBL3908600
6.96	IC50	110	nM	CHEMBL3930654
6.85	IC50	140	nM	CHEMBL3967925
6.85	IC50	140	nM	CHEMBL3905763
6.77	IC50	170	nM	CHEMBL3896688
6.75	IC50	180	nM	CHEMBL3965780
6.75	IC50	180	nM	CHEMBL3951510
6.72	IC50	190	nM	CHEMBL3899865
6.68	IC50	210	nM	CHEMBL3927512
6.66	IC50	220	nM	CHEMBL3941035
6.62	IC50	240	nM	CHEMBL3894011
6.62	IC50	240	nM	CHEMBL3933339
6.62	IC50	240	nM	CHEMBL3986145
6.62	IC50	240	nM	CHEMBL3911132
6.60	IC50	250	nM	CHEMBL3984483
6.60	IC50	250	nM	CHEMBL3912562
6.58	IC50	260	nM	CHEMBL3914321
6.54	IC50	290	nM	CHEMBL3949366
6.54	IC50	290	nM	CHEMBL3906562
6.54	IC50	290	nM	CHEMBL3960967
6.54	IC50	290	nM	CHEMBL3903792
6.50	IC50	320	nM	CHEMBL3963515
6.47	IC50	340	nM	CHEMBL3892216
6.46	IC50	350	nM	CHEMBL3918211
6.44	IC50	360	nM	CHEMBL3906656
6.41	IC50	390	nM	CHEMBL3972923
6.41	IC50	390	nM	CHEMBL3981009
6.41	IC50	390	nM	CHEMBL3906537
6.40	IC50	400	nM	CHEMBL3960018
6.38	IC50	420	nM	CHEMBL3959807
6.37	IC50	430	nM	CHEMBL3891041
6.35	IC50	450	nM	CHEMBL3979725
6.32	IC50	480	nM	CHEMBL3928828
6.32	IC50	480	nM	CHEMBL3913799
6.31	IC50	490	nM	CHEMBL3943719
6.31	IC50	490	nM	CHEMBL3986519

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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Barium	affects binding, decreases activity	1
Benzo(a)pyrene	increases methylation	1
Cesium	affects binding, decreases activity	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

26 unique, capped per target: 25 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

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1K1	PrecisION hKv12.2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice