KCNQ5

Summary

KCNQ5 (potassium voltage-gated channel subfamily Q member 5, HGNC:6299) is a protein-coding gene on chromosome 6q13, encoding Potassium voltage-gated channel subfamily KQT member 5 (Q9NR82). Pore-forming subunit of the voltage-gated potassium (Kv) channel broadly expressed in brain and involved in the regulation of neuronal excitability.

This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 56479 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal dominant 46 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 23
• Clinical variants (ClinVar): 885 total — 20 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_019842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6299
Approved symbol	KCNQ5
Name	potassium voltage-gated channel subfamily Q member 5
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	Kv7.5
Ensembl gene	ENSG00000185760
Ensembl biotype	protein_coding
OMIM	607357
Entrez	56479

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000342056, ENST00000355194, ENST00000370392, ENST00000370398, ENST00000403813, ENST00000414165, ENST00000427928, ENST00000441538, ENST00000443915, ENST00000445310, ENST00000628967, ENST00000629977, ENST00000692515, ENST00000692956

RefSeq mRNA: 5 — MANE Select: NM_019842 NM_001160130, NM_001160132, NM_001160133, NM_001160134, NM_019842

CCDS: CCDS4976, CCDS55034, CCDS55035, CCDS55037

Canonical transcript exons

ENST00000370398 — 14 exons

Exon	Start	End
ENSE00001295584	73077762	73077887
ENSE00001297383	73041936	73042062
ENSE00001303421	73003908	73003998
ENSE00001303940	73169746	73169854
ENSE00001304878	73192565	73192691
ENSE00001306025	73124486	73124512
ENSE00001315237	73190573	73190704
ENSE00001315454	73077322	73077497
ENSE00001326399	73120483	73120577
ENSE00001376844	73133421	73133641
ENSE00001452589	73194452	73198853
ENSE00001452621	72622064	72622587
ENSE00002021875	73105257	73105367
ENSE00002099238	73111308	73111403

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 97.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1412 / max 238.3430, expressed in 971 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68550	1.2873	453
68549	0.6893	276
68548	0.6050	316
68546	0.5779	210
68551	0.3408	159
68552	0.1594	87
68543	0.1439	69
68545	0.1378	58
68553	0.0945	45
68544	0.0598	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.24	gold quality
pons	UBERON:0000988	96.75	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.58	gold quality
tibialis anterior	UBERON:0001385	94.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.73	gold quality
deltoid	UBERON:0001476	94.47	gold quality
quadriceps femoris	UBERON:0001377	92.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.21	gold quality
vastus lateralis	UBERON:0001379	92.12	gold quality
superior frontal gyrus	UBERON:0002661	91.50	gold quality
primary visual cortex	UBERON:0002436	91.19	gold quality
middle temporal gyrus	UBERON:0002771	90.45	gold quality
postcentral gyrus	UBERON:0002581	90.25	gold quality
skeletal muscle tissue	UBERON:0001134	89.90	gold quality
parietal lobe	UBERON:0001872	89.83	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.39	gold quality
occipital lobe	UBERON:0002021	89.16	gold quality
biceps brachii	UBERON:0001507	88.92	gold quality
prefrontal cortex	UBERON:0000451	88.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.94	gold quality
frontal cortex	UBERON:0001870	86.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.51	gold quality
neocortex	UBERON:0001950	85.37	gold quality
gastrocnemius	UBERON:0001388	84.84	gold quality
muscle of leg	UBERON:0001383	84.09	gold quality
cerebral cortex	UBERON:0000956	83.88	gold quality
cartilage tissue	UBERON:0002418	83.51	gold quality
cortical plate	UBERON:0005343	83.31	gold quality
muscle tissue	UBERON:0002385	83.10	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	4121.60
E-HCAD-35	yes	3240.66
E-HCAD-25	yes	2011.15
E-HCAD-30	no	2658.94
E-ANND-3	no	4.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NEUROD1, RORB, SP1

miRNA regulators (miRDB)

191 targeting KCNQ5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-539-3P	99.98	70.74	1616

Literature-anchored findings (GeneRIF, showing 23)

• Src associates with KCNQ2-5 subunits but phosphorylates only KCNQ3-5. (PMID:15304482)
• In conclusion, this work demonstrates that inactivation is a key regulatory mechanism of Kv7.4 and Kv7.5 channels. (PMID:17237198)
• among the allowed assembly conformations are KCNQ3/4 and KCNQ4/5 heteromers. (PMID:18786918)
• While KCNE1 slows activation and suppresses inward rectification, KCNE3 drastically inhibits KCNQ5 currents. (PMID:19910673)
• Data show that KCNQ1 mRNA expression was increased and KCNQ5 decreased in the preterm preeclamptic women. (PMID:21730298)
• The results of this study indicated that Kv7.5 contributes to the spatial regulation of KCNE3. (PMID:22190306)
• characterized the cell-type specific spatial organization of the kcnq5 gene locus mediated by CTCF in detail using chromosome conformation capture (3C) and 3C-derived techniques (PMID:22347474)
• Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. (PMID:24297175)
• Kv7.1/Kv7.5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity. The lipid raft localization of Kv7.1/Kv7.5 heteromers provides efficient spatial and temporal regulation of smooth muscle function. (PMID:24855057)
• rs9351963 in KCNQ5 is a possible predictive factor of incidence of diarrhea in cancer patients treated with irinotecan chemotherapy. (PMID:25127363)
• suggestive loci for periodontitis: KCNQ5 on chromosome 6q13 in a Japanese population. study should contribute to further understanding of genetic factors for enhanced susceptibility to periodontitis. (PMID:25672891)
• Tannic acid activates Kv7.4 and Kv7.3/7.5 K(+) channels resulting in vasodilation. (PMID:26969140)
• These findings provide the first evidence linking PKC activation to suppression of Kv7 currents, membrane depolarization, and Ca(2+) influx via L-type voltage-sensitive Ca(2+) channels as a mechanism for histamine-induced bronchoconstriction. (PMID:28283479)
• both loss-of-function and gain-of-function KCNQ5 mutations, associated with increased excitability and decreased repolarization reserve, lead to pathophysiology. (PMID:28669405)
• Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia. (PMID:28884119)
• identified P2RX2, KCNQ5, ERBB3 and SOCS3 to be associated with the progression of age-related hearing impairment (PMID:29325454)
• Phylogenetic analysis, electrostatic potential mapping, in silico docking, electrophysiology, and radioligand binding assays reveal that the anticonvulsant binding pocket evolved to accommodate endogenous neurotransmitters including gamma-aminobutyric acid, which directly activates KCNQ5 and KCNQ3 via W265. (PMID:29748663)
• Phosphorylation of S53 on the amino terminus of Kv7.5 is essential for protein kinase A-dependent enhancement of channel activity in response to beta adrenergic receptor activation in vascular and airway smooth muscle cells. (PMID:30061510)
• Distinct functional domains were identified that confer differential sensitivities of Kv7.5 and Kv7.4 to stimulatory and inhibitory signaling. (PMID:31871302)
• Remodeling of Kv7.1 and Kv7.5 Expression in Vascular Tumors. (PMID:32825637)
• Gain of function due to increased opening probability by two KCNQ5 pore variants causing developmental and epileptic encephalopathy. (PMID:35377796)
• Human KCNQ5 de novo mutations underlie epilepsy and intellectual disability. (PMID:35583973)
• Loss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies. (PMID:36088682)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnq5b	ENSDARG00000069953
danio_rerio	kcnq5a	ENSDARG00000069954
mus_musculus	Kcnq5	ENSMUSG00000028033
rattus_norvegicus	Kcnq5	ENSRNOG00000013781

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), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily KQT member 5 — Q9NR82 (reviewed: Q9NR82)

Alternative names: KQT-like 5, Potassium channel subunit alpha KvLQT5, Voltage-gated potassium channel subunit Kv7.5

All UniProt accessions (5): Q9NR82, A6PVT7, A6PVT8, F8WEA4, H0Y3Z0

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of the voltage-gated potassium (Kv) channel broadly expressed in brain and involved in the regulation of neuronal excitability. Associates with KCNQ3/Kv7.3 pore-forming subunit to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. Contributes, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current. Also forms a functional channel with KCNQ1/Kv7.1 subunit that may contribute to vasoconstriction and hypertension. Channel may be selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) = Rb(+) > Cs(+) > Na(+). Similar to the native M-channel, KCNQ3-KCNQ5 potassium channel is suppressed by activation of the muscarinic acetylcholine receptor CHRM1.

Subunit / interactions. Homotetramer; forms a functional homotetrameric channel resulting in the expression of a small M-current. Heterotetramer with KCNQ3; forms heterotetrameric M-channel responsible for the native M-current. Heterotetramer with KCNQ1; forms a functional voltage-gated potassium channel. Interacts (via C-terminus) with calmodulin/CALM1; forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry); the interaction is calcium-independent, constitutive and participates in the channel function.

Subcellular location. Cell membrane.

Tissue specificity. Strongly expressed in brain and skeletal muscle. In brain, expressed in cerebral cortex, occipital pole, frontal lobe and temporal lobe. Lower levels in hippocampus and putamen. Low to undetectable levels in medulla, cerebellum and thalamus.

Disease relevance. Intellectual developmental disorder, autosomal dominant 46 (MRD46) [MIM:617601] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD46 patients manifest developmental delay and mild to moderate intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphatidylinositol-4,5-bisphosphate (PIP2) is essential to activate KCNQ5 channel by inducing the coupling of the voltage-sensing domain (VSD) and the pore-forming domain (PD). Calcium suppresses KCNQ5 channel current through calcium-bound CALM C-terminus. Therefore CALM acts as calcium sensor that controls channel activity. Activated by niflumic acid and the anticonvulsant retigabine. Inhibited by barium, linopirdine, XE991 and tetraethylammonium (as homomer). Insensitive to tetraethylammonium in KCNQ3-KCNQ5 heteromers.

Domain organisation. Each channel subunit contains six transmembrane segments (S1-S6) with S1-S4 forming one voltage sensing domain (VSD) and S5-S6 contributing to form one quarter of an interlocking pore-forming domain (PD). The CALM binding domains correspond to the first two membrane-proximal helical regions that interact with a single calmodulin/CALM molecule forming a clamp-like structure and are essential for channel trafficking and electrophysiological activity. CALM N-terminus binds to the second helix in both calcium-free and calcium-bound forms and regulates channel trafficking. CALM C-terminus binds to the first helice in calcium-free form; this interaction is disrupted by calcium binding which regulates channel electrophysiological activity. The C-terminal assembly domain carries the major determinants of tetramerization and subunit assembly specificity. Its coiled-coil region is four-stranded.

Similarity. Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.5/KCNQ5 sub-subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9NR82-1	1	yes
Q9NR82-2	2
Q9NR82-3	3
Q9NR82-4	4
Q9NR82-5	5
Q9NR82-6	6
Q9NR82-7	7

RefSeq proteins (5): NP_001153602, NP_001153604, NP_001153605, NP_001153606, NP_062816* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003937	K_chnl_volt-dep_KCNQ	Family
IPR005821	Ion_trans_dom	Domain
IPR013821	K_chnl_volt-dep_KCNQ_C	Domain

Pfam: PF00520, PF03520

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (54 total): topological domain 8, splice variant 7, sequence conflict 7, transmembrane region 6, sequence variant 6, region of interest 5, compositionally biased region 4, binding site 3, modified residue 3, helix 3, chain 1, intramembrane region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9J38	ELECTRON MICROSCOPY	2.4
6B8Q	X-RAY DIFFRACTION	2.6
9LJ5	ELECTRON MICROSCOPY	2.9
9LIZ	ELECTRON MICROSCOPY	3.1
9LJ1	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR82-F1	57.47	0.20

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 (3): 248; 264; 361

Post-translational modifications (3): 88, 447, 831

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: 253 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_POTASSIUM_ION_TRANSPORT, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GCANCTGNY_MYOD_Q6, MEF2_02, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, FOXD3_01, GOBP_MONOATOMIC_CATION_TRANSPORT, NFKB_C

GO Biological Process (6): potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (5): voltage-gated potassium channel activity (GO:0005249), voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099508), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), clathrin coat (GO:0030118), presynaptic membrane (GO:0042734), calyx of Held (GO:0044305), 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
potassium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
regulation of membrane potential	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
voltage-gated monoatomic ion channel activity	1
presynaptic membrane	1
regulation of presynaptic membrane potential	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
membrane coat	1
synaptic membrane	1
presynapse	1
axon terminus	1
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

2146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNQ5	KCNQ3	O43525	984
KCNQ5	KCNQ2	O43526	966
KCNQ5	KCNE4	Q8WWG9	893
KCNQ5	KCNQ4	P56696	761
KCNQ5	KCNQ1	P51787	714
KCNQ5	KCNE1	P15382	664
KCNQ5	CALM1	P02593	606
KCNQ5	CALML3	P27482	588
KCNQ5	CALML5	Q9NZT1	588
KCNQ5	PRSS56	P0CW18	584
KCNQ5	KCNMA1	Q12791	582
KCNQ5	C9orf50	Q5SZB4	579
KCNQ5	CALML6	Q8TD86	573
KCNQ5	CALML4	Q96GE6	572
KCNQ5	ANK3	Q12955	532
KCNQ5	KCNE3	Q9Y6H6	532

IntAct

28 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
KCNQ5	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
HCCS	MPZL1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	PLEKHG3	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
DISC1	KCNQ5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-MS), KCNQ5 (Affinity Capture-RNA), KCNQ5 (Affinity Capture-Western), KCNQ3 (Affinity Capture-Western), KCNQ5 (Protein-RNA), KCNQ5 (Proximity Label-MS), KCNQ5 (Proximity Label-MS), KCNQ5 (Proximity Label-MS), KCNQ5 (Proximity Label-MS)

ESM2 similar proteins: A2ARP9, A2ASI5, B1AWN6, B1AYL1, F1LQQ7, O08562, O46669, O70344, O73925, O88420, O88457, O88944, O97531, P02719, P04775, P08104, P0DMA5, P15389, P15390, P35499, P51787, P59111, P97414, Q01118, Q14524, Q28371, Q28644, Q2XVR7, Q62205, Q62968, Q6AXP6, Q6QIY3, Q7RTX7, Q8K3F6, Q96L42, Q96P56, Q99250, Q9ER60, Q9JJV9, Q9JK45

Diamond homologs: A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, B2RQA1, G5EFC3, O15554, O18868, O35173, O35174, O43525, O43526, O70344, O73606, O73925, O88758, O88759, O88943, O88944, O89109, O97531, P08510, P0A333, P0A334, P10499, P15384, P15387, P16388, P16389, P16390, P17658, P17659

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	KCNQ5	phosphorylation
KCNQ5	“up-regulates quantity”	potassium(1+)	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	253.8×	1e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	223.9×	2e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	223.9×	2e-14
Activation of BH3-only proteins	7	165.5×	2e-13
RHO GTPases activate PKNs	7	105.7×	6e-12
Intrinsic Pathway for Apoptosis	7	97.6×	9e-12
FOXO-mediated transcription	5	80.0×	3e-08
SARS-CoV-1-host interactions	7	58.6×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	73.3×	6e-07
intracellular protein localization	7	29.3×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	12
Uncertain significance	378
Likely benign	324
Benign	84

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072107	NM_019842.4(KCNQ5):c.1105C>T (p.Pro369Ser)	Pathogenic
1334356	NM_019842.4(KCNQ5):c.560G>A (p.Arg187Gln)	Pathogenic
1361599	NM_019842.4(KCNQ5):c.282_291del (p.Ser95fs)	Pathogenic
1675172	NM_019842.4(KCNQ5):c.824dup (p.Leu275fs)	Pathogenic
2121310	NM_019842.4(KCNQ5):c.559C>T (p.Arg187Ter)	Pathogenic
2571253	NM_019842.4(KCNQ5):c.769del (p.Ser257fs)	Pathogenic
2752272	NM_019842.4(KCNQ5):c.51G>A (p.Trp17Ter)	Pathogenic
2793965	NM_019842.4(KCNQ5):c.642_645del (p.Ile214fs)	Pathogenic
2809936	NM_019842.4(KCNQ5):c.84dup (p.Gly29fs)	Pathogenic
2854702	NM_019842.4(KCNQ5):c.2T>C (p.Met1Thr)	Pathogenic
2876968	NM_019842.4(KCNQ5):c.739C>T (p.Arg247Ter)	Pathogenic
3246150	NC_000006.11:g.(?73331918)(73905137_?)del	Pathogenic
3381895	NM_019842.4(KCNQ5):c.966G>A (p.Trp322Ter)	Pathogenic
3661308	NM_019842.4(KCNQ5):c.253del (p.Ala85fs)	Pathogenic
431385	NM_019842.4(KCNQ5):c.434T>G (p.Val145Gly)	Pathogenic
431386	NM_019842.4(KCNQ5):c.1021C>A (p.Leu341Ile)	Pathogenic
431387	NM_019842.4(KCNQ5):c.1286G>T (p.Ser429Ile)	Pathogenic
431388	NM_019842.4(KCNQ5):c.1106C>G (p.Pro369Arg)	Pathogenic
802242	NM_019842.4(KCNQ5):c.1106C>A (p.Pro369Gln)	Pathogenic
975567	NM_019842.4(KCNQ5):c.1040G>C (p.Gly347Ala)	Pathogenic
2305290	NM_019842.4(KCNQ5):c.1287C>A (p.Ser429Arg)	Likely pathogenic
2500718	NM_019842.4(KCNQ5):c.545C>T (p.Ala182Val)	Likely pathogenic
2775437	NM_019842.4(KCNQ5):c.1667G>C (p.Gly556Ala)	Likely pathogenic
3019100	NM_019842.4(KCNQ5):c.1248-3570T>C	Likely pathogenic
3067511	NM_019842.4(KCNQ5):c.1075C>T (p.Arg359Cys)	Likely pathogenic
3220891	NM_019842.4(KCNQ5):c.273del (p.Lys92fs)	Likely pathogenic
3572863	NM_019842.4(KCNQ5):c.1408C>T (p.Arg470Ter)	Likely pathogenic
4074723	NM_019842.4(KCNQ5):c.1631A>G (p.Tyr544Cys)	Likely pathogenic
4077061	NM_019842.4(KCNQ5):c.1051G>T (p.Ala351Ser)	Likely pathogenic
521883	NM_019842.4(KCNQ5):c.1039G>A (p.Gly347Ser)	Likely pathogenic

SpliceAI

5235 predictions. Top by Δscore:

Variant	Effect	Δscore
6:72622583:TTCGT:T	donor_gain	1.0000
6:72622584:TCGT:T	donor_gain	1.0000
6:72622585:CGTG:C	donor_loss	1.0000
6:72622586:GT:G	donor_gain	1.0000
6:72622587:TGTG:T	donor_loss	1.0000
6:72622588:G:GA	donor_loss	1.0000
6:72622588:G:GG	donor_gain	1.0000
6:72759270:GCT:G	donor_gain	1.0000
6:72937423:A:T	donor_gain	1.0000
6:73042024:G:GT	donor_gain	1.0000
6:73077493:GCAAG:G	donor_gain	1.0000
6:73077823:ATCT:A	acceptor_gain	1.0000
6:73077826:T:TA	acceptor_gain	1.0000
6:73077888:G:GG	donor_gain	1.0000
6:73111304:CCAG:C	acceptor_loss	1.0000
6:73111305:CA:C	acceptor_loss	1.0000
6:73111306:A:AG	acceptor_gain	1.0000
6:73111306:AG:A	acceptor_gain	1.0000
6:73111306:AGG:A	acceptor_gain	1.0000
6:73111307:G:GT	acceptor_gain	1.0000
6:73111307:GG:G	acceptor_gain	1.0000
6:73111307:GGG:G	acceptor_gain	1.0000
6:73111307:GGGC:G	acceptor_gain	1.0000
6:73111307:GGGCA:G	acceptor_gain	1.0000
6:73111401:CAG:C	donor_loss	1.0000
6:73111402:AGG:A	donor_loss	1.0000
6:73111403:GGT:G	donor_loss	1.0000
6:73111404:G:C	donor_loss	1.0000
6:73120458:A:AG	acceptor_gain	1.0000
6:73120459:T:G	acceptor_gain	1.0000

AlphaMissense

6051 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:73003927:T:C	C140R	1.000
6:73003988:T:C	L160P	1.000
6:73041936:G:A	E164K	1.000
6:73041946:T:G	M167R	1.000
6:73041957:T:C	F171L	1.000
6:73041959:T:A	F171L	1.000
6:73041959:T:G	F171L	1.000
6:73041960:G:C	G172R	1.000
6:73041966:G:A	E174K	1.000
6:73041967:A:T	E174V	1.000
6:73042023:G:A	G193R	1.000
6:73042023:G:C	G193R	1.000
6:73042035:T:C	F197L	1.000
6:73042036:T:C	F197S	1.000
6:73042036:T:G	F197C	1.000
6:73042037:T:A	F197L	1.000
6:73042037:T:G	F197L	1.000
6:73042062:G:C	D206H	1.000
6:73077322:A:C	D206A	1.000
6:73077322:A:G	D206G	1.000
6:73077322:A:T	D206V	1.000
6:73077331:T:A	V209D	1.000
6:73077340:C:A	A212D	1.000
6:73077402:A:C	S233R	1.000
6:73077404:T:A	S233R	1.000
6:73077404:T:G	S233R	1.000
6:73077411:T:C	F236L	1.000
6:73077412:T:C	F236S	1.000
6:73077412:T:G	F236C	1.000
6:73077413:C:A	F236L	1.000

dbSNP variants (sampled 300 via entrez): RS1000005189 (6:72704459 C>T), RS1000007007 (6:73121795 T>A), RS1000007224 (6:72648539 G>A), RS1000009264 (6:73014839 C>CTA), RS1000010168 (6:72870549 C>A), RS1000014463 (6:72806707 G>A), RS1000021894 (6:72937207 C>A), RS1000027256 (6:73191497 C>T), RS1000039100 (6:72890701 T>C,G), RS1000042635 (6:72693379 A>G), RS1000043261 (6:73071321 A>G), RS1000043992 (6:73169520 T>C), RS1000048612 (6:72800369 G>A,C), RS1000051423 (6:72659089 T>C), RS1000051726 (6:72746512 G>A)

Disease associations

OMIM: gene MIM:607357 | disease phenotypes: MIM:617601

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 46	Strong	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

Mondo (6): intellectual disability, autosomal dominant 46 (MONDO:0030911), hereditary ataxia (MONDO:0100309), prostate cancer (MONDO:0008315), primary ovarian failure (MONDO:0005387), intellectual disability (MONDO:0001071), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (5): Hereditary ataxia (Orphanet:183518), Familial prostate cancer (Orphanet:1331), Autosomal dominant non-syndromic intellectual disability (Orphanet:178469), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0002317	Unsteady gait
HP:0002384	Focal impaired awareness seizure
HP:0003593	Infantile onset
HP:0011463	Childhood onset
HP:0012444	Brain atrophy
HP:0012469	Infantile spasms
HP:0025116	Fetal distress
HP:0032792	Tonic seizure
HP:0033454	Tube feeding
HP:0200134	Epileptic encephalopathy

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001858_22	Refractive error	4.000000e-09
GCST002781_1	Periodontitis	5.000000e-06
GCST002976_3	HIV-1 viral setpoint	2.000000e-06
GCST003455_18	Spherical equivalent (joint analysis main effects and education interaction)	9.000000e-16
GCST003455_41	Spherical equivalent (joint analysis main effects and education interaction)	4.000000e-19
GCST003997_49	Myopia	2.000000e-63
GCST004162_18	Carotid plaque burden	6.000000e-07
GCST004185_9	Lung function (FEV1/FVC)	1.000000e-17
GCST004640_21	Western dietary pattern	9.000000e-06
GCST005790_70	Rosacea symptom severity	6.000000e-06
GCST006284_16	Plasma proprotein convertase subtilisin/kexin type 9 levels in stable coronary artery disease	2.000000e-07
GCST006291_129	Spherical equivalent or myopia (age of diagnosis)	5.000000e-48
GCST006443_6	Total body bone mineral density	6.000000e-06
GCST006522_21	Upper eyelid sagging severity	7.000000e-06
GCST006629_55	Pulse pressure	2.000000e-21
GCST007429_17	Lung function (FVC)	4.000000e-06
GCST007430_76	Peak expiratory flow	1.000000e-11
GCST007431_143	Lung function (FEV1/FVC)	5.000000e-31
GCST009209_5	Frontal pole volume	8.000000e-06
GCST009462_65	Optic disc size	1.000000e-15
GCST009962_9	High myopia	3.000000e-11
GCST010002_326	Refractive error	3.000000e-205
GCST90014268_15	Cataracts	4.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006319	HIV viral set point measurement
EFO:0004784	self reported educational attainment
EFO:0006501	carotid plaque build
EFO:0004713	FEV/FVC ratio
EFO:0008111	diet measurement
EFO:0009180	rosacea severity measurement
EFO:0006899	PCSK9 protein measurement
EFO:0004847	age at onset
EFO:0005763	pulse pressure measurement
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2362996 (PROTEIN FAMILY), CHEMBL2363063 (PROTEIN FAMILY), CHEMBL2925 (SINGLE PROTEIN), CHEMBL3883311 (PROTEIN COMPLEX), CHEMBL4523611 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,070 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL41355	EZOGABINE	4	3,996
CHEMBL266510	FLINDOKALNER	3	74

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9351963	Toxicity	3	irinotecan	Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9351963	KCNQ5	3	0.00	1	irinotecan

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
gabapentin	Activation	8.72	pEC50
retigabine derivative 10g	Activator	6.0	pEC50
flindokalner	Activator	5.6	pEC50
zinc pyrithione	Activator	5.0	pEC50
retigabine	Activator	5.0	pEC50
linopirdine	Inhibitor	4.8	pKd
XE991	Inhibitor	4.2	pIC50
tetraethylammonium	Channel blocker	1.5	pIC50

ChEMBL bioactivities

24 potent at pChembl≥5 of 28 total, top 24 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
7.10	EC50	80	nM	CHEMBL4278049
6.70	EC50	200	nM	CHEMBL4288707
6.60	EC50	250	nM	CHEMBL4277250
6.46	EC50	350	nM	CHEMBL4457044
6.44	EC50	360	nM	CHEMBL4287894
6.40	EC50	400	nM	CHEMBL4287478
6.30	EC50	500	nM	CHEMBL1703636
6.27	EC50	540	nM	CHEMBL4549229
6.23	EC50	588	nM	CHEMBL3621437
6.10	EC50	800	nM	EZOGABINE
5.97	EC50	1070	nM	CHEMBL4545892
5.97	EC50	1060	nM	CHEMBL5185685
5.86	EC50	1370	nM	CHEMBL4438770
5.78	EC50	1680	nM	CHEMBL4588394
5.62	EC50	2400	nM	FLINDOKALNER
5.61	EC50	2430	nM	CHEMBL4450214
5.46	EC50	3450	nM	EZOGABINE
5.42	EC50	3780	nM	CHEMBL5200636
5.42	EC50	3780	nM	CHEMBL4458793
5.35	EC50	4500	nM	CHEMBL5178988
5.05	EC50	9000	nM	CHEMBL2047524
5.00	EC50	1e+04	nM	CHEMBL2047846

PubChem BioAssay actives

24 with measured affinity, of 150 total; 22 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
N-[(1R)-2-hydroxy-1-(3-methylsulfonylphenyl)ethyl]-5-(pentafluoro-lambda6-sulfanyl)-2-phenoxybenzamide	1414248: Activation of human Kv7.3/7.5 by patch clamp method	ec50	0.0800	uM
4,5-difluoro-N-[(1S)-1-(3-methylsulfonylphenyl)ethyl]-2-phenoxybenzamide	1414248: Activation of human Kv7.3/7.5 by patch clamp method	ec50	0.2000	uM
trans-(1S,2S)-5,5-difluoro-N-[(1R)-2-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl]-2-phenylcyclohexane-1-carboxamide	1414248: Activation of human Kv7.3/7.5 by patch clamp method	ec50	0.2500	uM
3,3-dimethyl-N-[1-[[4-(trifluoromethyl)phenyl]methyl]indol-5-yl]butanamide	1604643: Activation of human Kv7.5 expressed in CHO cells assessed as increase in channel current amplitude by whole cell patch clamp electrophysiology assay	ec50	0.3500	uM
trans-(1S,2S)-N-[(1R)-1-(3-chlorophenyl)-2-hydroxyethyl]-5,5-difluoro-2-phenylcyclohexane-1-carboxamide	1414248: Activation of human Kv7.3/7.5 by patch clamp method	ec50	0.3600	uM
trans-(1S,2S)-5,5-difluoro-2-phenyl-N-[(1S)-1-phenylethyl]cyclohexane-1-carboxamide	1414248: Activation of human Kv7.3/7.5 by patch clamp method	ec50	0.4000	uM
N-(2,4,6-trimethylphenyl)bicyclo[2.2.1]heptane-2-carboxamide	1414248: Activation of human Kv7.3/7.5 by patch clamp method	ec50	0.5000	uM
ethyl N-[2-amino-3-fluoro-4-[[6-(trifluoromethyl)-3-pyridinyl]methylamino]phenyl]carbamate	1861514: Agonist activity at Kv7.5 (unknown origin) expressed in CHO cells co-expressing GFP	ec50	0.5400	uM
N-[4,6-dimethoxy-2-(4-methoxypiperidin-1-yl)pyrimidin-5-yl]-3,3-dimethylbutanamide	1249424: Activation of human Kv7.3/7.5 expressed in CHOK1 cells	ec50	0.5880	uM
ethyl N-[2-amino-4-[(4-fluorophenyl)methylamino]phenyl]carbamate	1604643: Activation of human Kv7.5 expressed in CHO cells assessed as increase in channel current amplitude by whole cell patch clamp electrophysiology assay	ec50	0.8000	uM
ethyl N-[2-amino-3,5-difluoro-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]carbamate	1861514: Agonist activity at Kv7.5 (unknown origin) expressed in CHO cells co-expressing GFP	ec50	1.0600	uM
N-[1-[[4-(trifluoromethyl)phenyl]methyl]indol-5-yl]heptanamide	1604643: Activation of human Kv7.5 expressed in CHO cells assessed as increase in channel current amplitude by whole cell patch clamp electrophysiology assay	ec50	1.0700	uM
tert-butyl N-[2-(ethoxycarbonylamino)-4-[(4-fluorophenyl)methyl-prop-2-ynylamino]phenyl]carbamate	1586935: Agonist activity at human KCNQ5 expressed in CHOK1 cells by whole cell patch clamp assay	ec50	1.3700	uM
tert-butyl N-[2-(ethoxycarbonylamino)-5-[(4-fluorophenyl)methyl-prop-2-ynylamino]phenyl]carbamate	1586935: Agonist activity at human KCNQ5 expressed in CHOK1 cells by whole cell patch clamp assay	ec50	1.6800	uM
(3S)-3-(5-chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1H-indol-2-one	726084: Positive modulatory activity at voltage-gated K channel 7.5 (unknown origin)	ec50	2.4000	uM
tert-butyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynylamino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]carbamate	1586935: Agonist activity at human KCNQ5 expressed in CHOK1 cells by whole cell patch clamp assay	ec50	2.4300	uM
cyclopropyl N-[2-amino-3-fluoro-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]carbamate	1861514: Agonist activity at Kv7.5 (unknown origin) expressed in CHO cells co-expressing GFP	ec50	3.7800	uM
cyclopropyl N-[2-amino-3,5,6-trifluoro-4-[[3-fluoro-5-(trifluoromethyl)-2-pyridinyl]methylamino]phenyl]carbamate	1861514: Agonist activity at Kv7.5 (unknown origin) expressed in CHO cells co-expressing GFP	ec50	3.7800	uM
N-(2,4-dibromophenyl)-2-[[4-methyl-5-[(4-methylphenyl)methylsulfanylmethyl]-1,2,4-triazol-3-yl]sulfanyl]acetamide	1870621: Agonist activity at human KCNQ5 channel expressed in CHO cells assessed as increase in outward current by patch clamp electrophysiology method	ec50	4.5000	uM
4-chloro-N-(2-chloropyrimidin-5-yl)-3-fluorobenzamide	669437: Agonist activity at KCNQ3/KCNQ5 expressed in CHO cells increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	9.0000	uM
N-(2-chloropyrimidin-5-yl)-3-fluoro-4-methylbenzamide	669437: Agonist activity at KCNQ3/KCNQ5 expressed in CHO cells increase in KCl-induced 86Rb+ efflux incubated for 10 mins prior to KCl-induction by liquid scintillation counting	ec50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, decreases reaction, affects cotreatment	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
(+)-JQ1 compound	decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
N-(1-(3-morpholin-4-ylphenyl)ethyl)-3-phenylacrylamide	increases activity	1
bisphenol S	increases methylation	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Acetylcysteine	decreases expression, decreases reaction	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	decreases expression	1
Pesticides	affects methylation	1
Thallium	increases activity, affects binding, increases import	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1

ChEMBL screening assays

40 unique, capped per target: 35 binding, 2 functional, 2 admet, 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
CHEMBL1794443	Functional	PUBCHEM_BIOASSAY: Mode of action assay-Specificity test for the KCNQ2 activators in the KCNQ5 expressing cells. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2239, AID2258, AID2287]	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1KB	PrecisION hKv7.3/Kv7.5-HEK	Transformed cell line	Female
CVCL_D1KD	PrecisION hKv7.4/Kv7.5-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer