KCNH8

Summary

KCNH8 (potassium voltage-gated channel subfamily H member 8, HGNC:18864) is a protein-coding gene on chromosome 3p24.3, encoding Voltage-gated delayed rectifier potassium channel KCNH8 (Q96L42). Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents.

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 H. This member is a pore-forming (alpha) subunit.

Source: NCBI Gene 131096 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 147 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_144633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18864
Approved symbol	KCNH8
Name	potassium voltage-gated channel subfamily H member 8
Location	3p24.3
Locus type	gene with protein product
Status	Approved
Aliases	Kv12.1, elk3
Ensembl gene	ENSG00000183960
Ensembl biotype	protein_coding
OMIM	608260
Entrez	131096

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000328405, ENST00000452398, ENST00000475063, ENST00000938024

RefSeq mRNA: 1 — MANE Select: NM_144633 NM_144633

CCDS: CCDS2632

Canonical transcript exons

ENST00000328405 — 16 exons

Exon	Start	End
ENSE00001295800	19281198	19281329
ENSE00001299391	19148510	19148795
ENSE00001300020	19342587	19342714
ENSE00001300111	19451155	19451404
ENSE00001301382	19253654	19253887
ENSE00001324320	19450106	19450305
ENSE00001326716	19533395	19535642
ENSE00003486388	19517998	19518074
ENSE00003532935	19515322	19515428
ENSE00003538650	19438164	19438361
ENSE00003541902	19456768	19456982
ENSE00003595401	19347725	19347965
ENSE00003597538	19512970	19513325
ENSE00003603123	19510363	19510401
ENSE00003645883	19395104	19395311
ENSE00003677338	19390481	19390638

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 90.49.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5113 / max 162.8225, expressed in 285 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35642	1.3892	154
35644	0.4092	39
35641	0.2791	134
35640	0.2358	108
35639	0.1468	68
35646	0.0511	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	90.49	gold quality
endothelial cell	CL:0000115	85.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.75	gold quality
substantia nigra	UBERON:0002038	80.39	gold quality
pituitary gland	UBERON:0000007	80.37	gold quality
adenohypophysis	UBERON:0002196	79.83	gold quality
putamen	UBERON:0001874	79.80	gold quality
midbrain	UBERON:0001891	79.11	gold quality
spinal cord	UBERON:0002240	78.78	gold quality
Ammon’s horn	UBERON:0001954	78.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.96	gold quality
amygdala	UBERON:0001876	77.59	gold quality
inferior vagus X ganglion	UBERON:0005363	77.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.38	gold quality
ganglionic eminence	UBERON:0004023	77.22	gold quality
cortical plate	UBERON:0005343	76.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	76.60	gold quality
right frontal lobe	UBERON:0002810	76.31	gold quality
lateral globus pallidus	UBERON:0002476	76.28	gold quality
caudate nucleus	UBERON:0001873	76.11	gold quality
buccal mucosa cell	CL:0002336	74.84	silver quality
hypothalamus	UBERON:0001898	74.26	gold quality
primary visual cortex	UBERON:0002436	74.16	gold quality
forebrain	UBERON:0001890	73.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	73.87	gold quality
occipital lobe	UBERON:0002021	73.05	gold quality
ventricular zone	UBERON:0003053	72.53	gold quality
postcentral gyrus	UBERON:0002581	72.48	gold quality
temporal lobe	UBERON:0001871	72.25	gold quality
brain	UBERON:0000955	72.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1389.28
E-HCAD-35	yes	88.04
E-ANND-3	yes	5.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, EGR1

miRNA regulators (miRDB)

112 targeting KCNH8, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 1)

• Kv12.1 channels add to the growing list of K(+) channels that are insensitive to phospholipase C beta signaling (PMID:30136882)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnh8	ENSDARG00000062640
mus_musculus	Kcnh8	ENSMUSG00000035580
rattus_norvegicus	Kcnh8	ENSRNOG00000058626
drosophila_melanogaster	sei	FBGN0003353
drosophila_melanogaster	Elk	FBGN0011589
drosophila_melanogaster	CG6026	FBGN0038676
drosophila_melanogaster	CngA	FBGN0261612
drosophila_melanogaster	Cngl	FBGN0263257
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), KCNH3 (ENSG00000135519), HCN4 (ENSG00000138622), KCNH5 (ENSG00000140015), KCNH1 (ENSG00000143473), HCN3 (ENSG00000143630), CNGA3 (ENSG00000144191), HCN1 (ENSG00000164588), CNGB3 (ENSG00000170289), KCNH6 (ENSG00000173826), CNGA2 (ENSG00000183862), KCNH7 (ENSG00000184611), CNGA1 (ENSG00000198515)

Protein

Protein identifiers

Voltage-gated delayed rectifier potassium channel KCNH8 — Q96L42 (reviewed: Q96L42)

Alternative names: ELK1, Ether-a-go-go-like potassium channel 3, Potassium voltage-gated channel subfamily H member 8, Voltage-gated potassium channel subunit Kv12.1

All UniProt accessions (2): Q96L42, F8WCG6

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents. Elicits a slowly activating, non-inactivating and slowly deactivation outwards potassium current at depolarizating voltages from -30 mV to +50mV. Shows no obvious change in the activation rate from different holding potentials. Activation is strongly dependent on the pH of the external solution.

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.

Subcellular location. Membrane.

Tissue specificity. Primarily expressed in the nervous system.

Similarity. Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.1/KCNH8 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96L42-1	1	yes
Q96L42-2	2

RefSeq proteins (1): NP_653234* (*=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 (36 total): topological domain 8, transmembrane region 6, region of interest 5, splice variant 4, compositionally biased region 3, domain 2, glycosylation site 2, sequence variant 2, chain 1, intramembrane region 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96L42-F1	64.41	0.25

Functional residue map

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

Glycosylation sites (2): 320, 409

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: 453 (showing top): AHRARNT_01, GOBP_POTASSIUM_ION_TRANSPORT, MYOGENIN_Q6, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, TGCACTT_MIR519C_MIR519B_MIR519A, REACTOME_POTASSIUM_CHANNELS, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_WOUND_HEALING, GTGCCTT_MIR506, TCF4_Q5, AP1_Q4_01

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 (4): voltage-gated potassium channel activity (GO:0005249), delayed rectifier potassium channel activity (GO:0005251), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267)

GO Cellular Component (3): plasma membrane (GO:0005886), monoatomic ion channel complex (GO:0034702), membrane (GO:0016020)

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
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
voltage-gated potassium channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNH8	ELK4	P28323	966
KCNH8	ELK3	P41970	870
KCNH8	SRF	P11831	593
KCNH8	EGR1	P18146	498
KCNH8	KCNK17	Q96T54	496
KCNH8	TMC5	Q6UXY8	494
KCNH8	KCNC2	Q96PR1	493
KCNH8	DPY19L4	Q7Z388	462
KCNH8	AR	P10275	459
KCNH8	CACNA1C	Q13936	444
KCNH8	TMEM9B	Q9NQ34	444
KCNH8	CCNQ	Q8N1B3	438
KCNH8	NOC4L	Q9BVI4	433
KCNH8	VWA7	Q9Y334	432
KCNH8	CHMP6	Q96FZ7	425
KCNH8	IGHV4-38-2	P0DP08	425

IntAct

3 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350
FMR1	KCNH8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): KCNH8 (Affinity Capture-RNA), KCNH8 (Affinity Capture-MS), KCNH8 (Protein-peptide), KCNH8 (Negative Genetic), KCNH8 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1D5PXA5, O18784, O35119, O35433, O62852, P0C550, P19334, P34586, P34641, P48994, P48995, P69744, P79100, P97414, Q0JKV1, Q12324, Q5ICL9, Q61056, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q875M2, Q8GXE6, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q96L42, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9MYV9, Q9NQA5, Q9P2G1, Q9QUQ5, Q9QX01, Q9QX29

Diamond homologs: A0A364LYQ6, A5VUS1, A6X554, A9MBM8, A9WYQ7, B2SB67, O34627, O48963, O64511, O89047, P30663, P58724, P59111, P93025, Q01371, Q1M667, Q2NB77, Q2NB98, Q2QYY8, Q2R2W1, Q2RBR1, Q2YKK7, Q48IV1, Q4ZSY3, Q577Y7, Q5Z8K3, Q60603, Q63472, Q67UX0, Q881J7, Q8FW73, Q8LPD9, Q8W420, Q8YC53, Q92DM1, Q94BT6, Q96L42, Q9C9W9, Q9HPU8, Q9QWS8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	125
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1330209	GRCh37/hg19 3p24.3(chr3:18004128-19575641)x1	Pathogenic
1700685	NM_144633.3(KCNH8):c.298T>C (p.Tyr100His)	Likely pathogenic

SpliceAI

6007 predictions. Top by Δscore:

Variant	Effect	Δscore
12:96223560:TGCA:T	acceptor_loss	1.0000
12:96223564:GGT:G	acceptor_gain	1.0000
12:96223741:C:G	donor_gain	1.0000
12:96223771:AAGGT:A	donor_loss	1.0000
12:96223772:AGGTA:A	donor_loss	1.0000
12:96223774:GTAAA:G	donor_loss	1.0000
12:96223775:T:G	donor_loss	1.0000
12:96246938:A:AG	acceptor_gain	1.0000
12:96246939:G:GG	acceptor_gain	1.0000
12:96246939:GAAC:G	acceptor_gain	1.0000
3:19204958:G:GT	donor_gain	1.0000
3:19253650:ATAG:A	acceptor_loss	1.0000
3:19253652:A:AG	acceptor_gain	1.0000
3:19253653:G:A	acceptor_loss	1.0000
3:19253653:G:GG	acceptor_gain	1.0000
3:19253653:GATA:G	acceptor_gain	1.0000
3:19253884:AACGG:A	donor_loss	1.0000
3:19253887:GGTG:G	donor_loss	1.0000
3:19253888:G:GA	donor_loss	1.0000
3:19253889:T:G	donor_loss	1.0000
3:19281188:A:AG	acceptor_gain	1.0000
3:19281188:ACT:A	acceptor_gain	1.0000
3:19281189:C:G	acceptor_gain	1.0000
3:19281190:T:A	acceptor_gain	1.0000
3:19281193:T:A	acceptor_gain	1.0000
3:19281194:GCAG:G	acceptor_loss	1.0000
3:19281195:CAG:C	acceptor_loss	1.0000
3:19281196:A:AG	acceptor_gain	1.0000
3:19281196:AG:A	acceptor_gain	1.0000
3:19281196:AGG:A	acceptor_gain	1.0000

AlphaMissense

7277 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:19148755:C:A	N12K	1.000
3:19148755:C:G	N12K	1.000
3:19148759:T:C	F14L	1.000
3:19148760:T:C	F14S	1.000
3:19148760:T:G	F14C	1.000
3:19148761:C:A	F14L	1.000
3:19148761:C:G	F14L	1.000
3:19148763:T:A	L15Q	1.000
3:19148763:T:C	L15P	1.000
3:19148772:T:A	I18N	1.000
3:19148772:T:G	I18S	1.000
3:19148774:G:C	A19P	1.000
3:19148775:C:A	A19D	1.000
3:19148783:T:C	F22L	1.000
3:19148785:T:A	F22L	1.000
3:19148785:T:G	F22L	1.000
3:19253662:T:C	F29L	1.000
3:19253663:T:C	F29S	1.000
3:19253664:C:A	F29L	1.000
3:19253664:C:G	F29L	1.000
3:19253669:T:A	L31H	1.000
3:19253669:T:C	L31P	1.000
3:19253678:C:A	A34D	1.000
3:19253702:T:A	I42K	1.000
3:19253705:T:A	V43D	1.000
3:19253707:T:C	Y44H	1.000
3:19253712:T:G	C45W	1.000
3:19253714:C:T	S46F	1.000
3:19281212:T:C	C109R	1.000
3:19281234:T:A	I116K	1.000

dbSNP variants (sampled 300 via entrez): RS1000000770 (3:19258306 A>G), RS1000013548 (3:19338446 T>A), RS1000017018 (3:19381431 C>G,T), RS1000021220 (3:19267811 G>A), RS1000032150 (3:19258658 T>C), RS1000032912 (3:19469049 C>G,T), RS1000041424 (3:19175633 A>T), RS1000042821 (3:19530879 A>T), RS1000061847 (3:19147701 C>A,G,T), RS1000061879 (3:19466300 T>C,G), RS1000063873 (3:19398659 T>C), RS1000066965 (3:19279651 A>G), RS1000089349 (3:19417600 T>G), RS1000094637 (3:19311168 A>G), RS1000121069 (3:19470528 T>C,G)

Disease associations

OMIM: gene MIM:608260 | disease phenotypes: MIM:619228, MIM:254900, MIM:190300

GenCC curated gene-disease

Mondo (3): developmental delay with dysmorphic facies and dental anomalies (MONDO:0030988), action myoclonus-renal failure syndrome (MONDO:0009699), essential tremor (MONDO:0003233)

Orphanet (2): Action myoclonus-renal failure syndrome (Orphanet:163696), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000101_9	Hip geometry	4.000000e-06
GCST004162_14	Carotid plaque burden	1.000000e-06
GCST004343_2	Chronic venous disease	5.000000e-11
GCST004861_44	Itch intensity from mosquito bite	1.000000e-09
GCST005848_11	Heart rate response to recovery post exercise (50 sec)	8.000000e-09
GCST008295_3	Number of decayed, missing and filled tooth surfaces or use of dentures	9.000000e-10
GCST008306_34	Dentures	2.000000e-09
GCST011494_1	Daytime nap	5.000000e-12
GCST012485_3	Cerebral amyloid angiopathy x sex interaction in Alzheimer’s disease	1.000000e-06
GCST90000047_86	Age at first sexual intercourse	3.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004685	hip geometry
EFO:0006501	carotid plaque build
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0009185	heart rate response to recovery post exercise
EFO:0010078	dentures
EFO:0007828	daytime rest measurement
EFO:0008343	sex interaction measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350

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)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
Ba2+	Channel blocker	3.7	pIC50

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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	increases methylation	1
methyleugenol	decreases expression	1
bisphenol A	affects methylation	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
tobacco tar	decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
allyl sulfide	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Estradiol	decreases expression	1
Lead	decreases expression	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	decreases expression	1
Valproic Acid	affects expression	1
Okadaic Acid	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)

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

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT04880616	PHASE2	COMPLETED	Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor
NCT05021978	PHASE2	COMPLETED	A Clinical Trial of PRAX-944 in Participants With Essential Tremor
NCT05021991	PHASE2	COMPLETED	A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor
NCT05122650	PHASE2	COMPLETED	A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)
NCT05173012	PHASE2	COMPLETED	Study to Evaluate SAGE-324 in Participants With Essential Tremor
NCT05387642	PHASE2	WITHDRAWN	A Clinical Trial of PRAX-114 in Participants With Essential Tremor
NCT06312800	PHASE2	WITHDRAWN	Acamprosate and Methazolamide for Essential Tremor
NCT06821906	PHASE2	RECRUITING	Stereotactic Radiosurgery in the Treatment of Essential Tremor
NCT07074002	PHASE2	RECRUITING	Proof of Concept Study on BP1.4979 Effect on Essential Tremor
NCT07103265	PHASE2	NOT_YET_RECRUITING	Developing a New LIFU Neuromodulation Method to Suppress Tremor
NCT00001986	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT00016679	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT01304758	PHASE1	COMPLETED	ExAblate Transcranial MR Guided Focused Ultrasound in the Treatment of Essential Tremor