KCNC4

Summary

KCNC4 (potassium voltage-gated channel subfamily C member 4, HGNC:6236) is a protein-coding gene on chromosome 1p13.3, encoding Voltage-gated potassium channel KCNC4 (Q03721). Voltage-gated potassium channel that opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient.

The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. It generates atypical voltage-dependent transient current that may be important for neuronal excitability. Multiple transcript variants have been found for this gene.

Source: NCBI Gene 3749 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 118 total
• Druggable target: yes
• MANE Select transcript: NM_001039574

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6236
Approved symbol	KCNC4
Name	potassium voltage-gated channel subfamily C member 4
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Kv3.4, HKSHIIIC
Ensembl gene	ENSG00000116396
Ensembl biotype	protein_coding
OMIM	176265
Entrez	3749

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000369787, ENST00000412512, ENST00000413138, ENST00000438661, ENST00000459877, ENST00000469655, ENST00000489935, ENST00000636402

RefSeq mRNA: 4 — MANE Select: NM_001039574 NM_001039574, NM_001377330, NM_001377331, NM_004978

CCDS: CCDS44193, CCDS821, CCDS91021

Canonical transcript exons

ENST00000438661 — 4 exons

Exon	Start	End
ENSE00000826879	110222964	110223900
ENSE00001124219	110225975	110226178
ENSE00001450883	110210314	110212177
ENSE00003647349	110232911	110234044

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 87.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8192 / max 55.8084, expressed in 1308 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4530	1.8400	1038
4531	0.5208	272
4528	0.4864	226
4532	0.3458	183
4533	0.3400	173
4529	0.1594	59
4534	0.1267	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	87.43	gold quality
cingulate cortex	UBERON:0003027	85.46	gold quality
prefrontal cortex	UBERON:0000451	85.40	gold quality
anterior cingulate cortex	UBERON:0009835	85.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.09	gold quality
amygdala	UBERON:0001876	84.99	gold quality
cerebellar hemisphere	UBERON:0002245	84.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.95	gold quality
cerebellar cortex	UBERON:0002129	83.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.59	gold quality
neocortex	UBERON:0001950	82.72	gold quality
frontal cortex	UBERON:0001870	82.55	gold quality
hypothalamus	UBERON:0001898	82.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.01	gold quality
cerebellum	UBERON:0002037	81.65	gold quality
cerebral cortex	UBERON:0000956	81.18	gold quality
oocyte	CL:0000023	80.81	gold quality
temporal lobe	UBERON:0001871	80.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.07	gold quality
apex of heart	UBERON:0002098	79.73	gold quality
primary visual cortex	UBERON:0002436	79.36	gold quality
Ammon’s horn	UBERON:0001954	79.05	gold quality
telencephalon	UBERON:0001893	78.53	gold quality
forebrain	UBERON:0001890	78.51	gold quality
brain	UBERON:0000955	78.38	gold quality
thoracic aorta	UBERON:0001515	78.36	gold quality
ascending aorta	UBERON:0001496	78.33	gold quality
aorta	UBERON:0000947	78.17	gold quality
popliteal artery	UBERON:0002250	78.16	gold quality
central nervous system	UBERON:0001017	78.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.79
E-GEOD-124858	no	67.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting KCNC4, 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-8485	100.00	77.57	4731
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615

Literature-anchored findings (GeneRIF, showing 11)

• Kv3.4 was overexpressed in early stages of Alzheimer disease and in advanced stages was present at high levels in neurodegenerative structures. This subunit regulates delayed-rectifier currents, primary determinants of spike repolarization in neurones (PMID:15485486)
• The characterization of a missense mutation in MiRP2 that affects its phosphorylation and consequent interactions with Kv3.4 is reported. (PMID:16449802)
• Kv3.4 channels exert a permissive role in the cell cycle progression of proliferating uterine vascular smooth cells. (PMID:20093253)
• Although all KV3 subunit transcripts are significantly expressed at embryonic age in whole mouse brain extracts, only KV3.1, KV3.2 and KV3.4 subunit transgenic proteins are present. (PMID:21912965)
• these data suggest that Kv3.4 and Cav1.2 may act together to control Ca(2) -dependent electrical activity of pioneer axons and play important roles during axon pathfinding. (PMID:22473424)
• Ionizing radiation-induced G2/M arrest was preceded by activation of Kv3.4-like voltage-gated potassium channels. (PMID:23443853)
• These results suggest a novel peripheral mechanism of post-spinal cord injury pain sensitization implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic interventions. (PMID:25609640)
• This study provides original evidence to demonstrate the early occurrence and high prevalence of abnormal Kv3.4 expression in oral leucoplakias. Our results support a role for Kv3.4 potassium channel in OSCC tumorigenesis rather than tumour progression and disease outcome. (PMID:26648458)
• HIF-1alpha regulates the invasion, migration and proliferation of oral cancer cells by regulating Kv3.4 expression. (PMID:31471334)
• PKCepsilon associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner. (PMID:33368632)
• Tunable Action Potential Repolarization Governed by Kv3.4 Channels in Dorsal Root Ganglion Neurons. (PMID:36198500)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcnc4	ENSMUSG00000027895
rattus_norvegicus	Kcnc4	ENSRNOG00000060988

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNV2 (ENSG00000168263), KCNG4 (ENSG00000168418), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Voltage-gated potassium channel KCNC4 — Q03721 (reviewed: Q03721)

Alternative names: KSHIIIC, Potassium voltage-gated channel subfamily C member 4, Voltage-gated potassium channel subunit Kv3.4

All UniProt accessions (3): A0A1B0GVB7, Q03721, H7BZ66

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated potassium channel that opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics.

Subunit / interactions. Homotetramer. Heterotetramer of potassium channel proteins.

Subcellular location. Membrane.

Post-translational modifications. Phosphorylation of serine residues in the inactivation gate inhibits rapid channel closure.

Domain organisation. The cytoplasmic N-terminus mediates N-type inactivation. Composed of the tetramerization T1 domain, six membrane spanning regions including voltage-sensing (S1-S4) and pore domains (S5- S6) and a variable C-terminal domain.

Miscellaneous. Could be a cloning artifact.

Similarity. Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.4/KCNC4 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q03721-1	1	yes
Q03721-2	2
Q03721-3	3

RefSeq proteins (4): NP_001034663, NP_001364259, NP_001364260, NP_004969 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003974	K_chnl_volt-dep_Kv3	Family
IPR005405	K_chnl_volt-dep_Kv3.4	Family
IPR005821	Ion_trans_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR021645	Shal-type_N	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family

Pfam: PF00520, PF02214, PF11601

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (51 total): binding site 8, mutagenesis site 8, transmembrane region 6, topological domain 4, region of interest 4, modified residue 4, splice variant 3, sequence variant 3, glycosylation site 2, sequence conflict 2, turn 2, strand 2, chain 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1B4G	SOLUTION NMR
1B4I	SOLUTION NMR
1ZTN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03721-F1	69.04	0.29

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 (8): 116; 122; 143; 144; 436; 437; 438; 439

Post-translational modifications (4): 8, 9, 15, 21

Glycosylation sites (2): 256, 265

Mutagenesis-validated functional residues (8):

Position	Phenotype
8	decreased inhibition of channel closure by pkc. inhibition of channel closure is nearly abolished; when associated with
8	decreased rate of channel inactivation. loss of channel inactivation; when associated with d-9; d-15 and d-21.
9	strong decrease of inhibition of channel closure by pkc. inhibition of channel closure is nearly abolished; when associa
9	decreased rate of channel inactivation. loss of channel inactivation; when associated with d-8; d-15 and d-21.
15	decreased inhibition of channel closure by pkc.
15	slightly decreased rate of channel inactivation. loss of channel inactivation; when associated with d-8; d-9 and d-21.
21	decreased inhibition of channel closure by pkc.
21	slightly decreased rate of channel inactivation. loss of channel inactivation; when associated with d-8; d-9 and d-15.

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: 160 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, MODULE_99, GOBP_SYNAPTIC_SIGNALING, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOCC_NEURON_PROJECTION, GOBP_TRANSMEMBRANE_TRANSPORT, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GOCC_NEURON_PROJECTION_TERMINUS

GO Biological Process (8): action potential (GO:0001508), potassium ion transport (GO:0006813), chemical synaptic transmission (GO:0007268), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (7): voltage-gated potassium channel activity (GO:0005249), delayed rectifier potassium channel activity (GO:0005251), potassium channel activity (GO:0005267), metal ion binding (GO:0046872), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), gated channel activity (GO:0022836)

GO Cellular Component (9): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), dendrite membrane (GO:0032590), neuronal cell body membrane (GO:0032809), presynaptic membrane (GO:0042734), axon terminus (GO:0043679), postsynaptic membrane (GO:0045211), 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
channel activity	2
synaptic membrane	2
presynapse	2
regulation of membrane potential	1
metal ion transport	1
anterograde trans-synaptic signaling	1
protein complex oligomerization	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 cation channel activity	1
potassium ion transmembrane transporter activity	1
cation binding	1
monoatomic ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
dendrite	1
neuron projection membrane	1
neuronal cell body	1
cell body membrane	1
neuron projection terminus	1
distal axon	1
postsynapse	1
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNC4	KCNE3	Q9Y6H6	909
KCNC4	KCNE4	Q8WWG9	837
KCNC4	KCNH2	Q12809	762
KCNC4	KCNE1	P15382	733
KCNC4	KCNAB2	Q13303	641
KCNC4	KCNE2	Q9Y6J6	620
KCNC4	KCNC1	P48547	599
KCNC4	SHPK	Q9UHJ6	557
KCNC4	KCTD5	Q9NXV2	556
KCNC4	KCND3	Q9UK17	545
KCNC4	KCNAB1	Q14722	533
KCNC4	KCNA4	P22459	505
KCNC4	KCNH3	Q9ULD8	494
KCNC4	KCND1	Q9NSA2	491
KCNC4	KCNJ12	Q14500	464

IntAct

9 interactions, top by confidence:

A	B	Type	Score
BACE1	KCNC4	psi-mi:“MI:0915”(physical association)	0.520
PCNA	KCNC4	psi-mi:“MI:0915”(physical association)	0.370
KCNC4	SMPD2	psi-mi:“MI:0914”(association)	0.350
KCNC4	HSPA2	psi-mi:“MI:0914”(association)	0.350
KCNC3	FYN	psi-mi:“MI:0914”(association)	0.350
TMEM67	PGRMC2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (63): KCNC4 (Proximity Label-MS), KCNC3 (Affinity Capture-MS), KCNC1 (Affinity Capture-MS), DNAJB5 (Affinity Capture-MS), SLC25A51 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), RHBDD1 (Affinity Capture-MS), RNF215 (Affinity Capture-MS), TYW1 (Affinity Capture-MS), AMFR (Affinity Capture-MS), ABCB10 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS)

ESM2 similar proteins: A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, D4ADX7, O35173, O35174, O88758, P15384, P15388, P16390, P17658, P17659, P19024, P22001, P22460, P22462, P25122, P48547, P50638, P59053, P59994, P79197, Q03719, Q03721, Q14B80, Q17ST2, Q61762, Q61923, Q63734, Q7TSH7, Q8CFS6, Q8R1C0

Diamond homologs: A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, G5EFC3, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16390, P17970, P17971, P17972, P22001, P22459, P22739, P25122, P48547, P59053, P59994, P59995

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
KCNC4	“down-regulates quantity”	potassium(1+)	relocalization
PRKCB	down-regulates	KCNC4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

506 predictions. Top by Δscore:

Variant	Effect	Δscore
1:110212176:GG:G	donor_gain	0.9900
1:110212177:GG:G	donor_gain	0.9900
1:110212178:G:GG	donor_gain	0.9900
1:110212178:GTGAG:G	donor_loss	0.9900
1:110212179:T:G	donor_loss	0.9900
1:110212180:GAGTG:G	donor_loss	0.9900
1:110225971:TCAG:T	acceptor_loss	0.9900
1:110225972:CA:C	acceptor_loss	0.9900
1:110225973:A:AC	acceptor_loss	0.9900
1:110225973:A:AG	acceptor_gain	0.9900
1:110225974:G:GG	acceptor_gain	0.9900
1:110225974:GA:G	acceptor_gain	0.9900
1:110225974:GACT:G	acceptor_gain	0.9900
1:110225974:GACTC:G	acceptor_gain	0.9900
1:110226165:T:TA	donor_gain	0.9900
1:110226166:A:AA	donor_gain	0.9900
1:110235212:GT:G	donor_gain	0.9900
1:110212080:G:T	donor_gain	0.9800
1:110223850:A:AG	donor_gain	0.9800
1:110225963:T:TA	acceptor_gain	0.9800
1:110225974:GAC:G	acceptor_gain	0.9800
1:110226176:AAGG:A	donor_loss	0.9800
1:110226177:AG:A	donor_loss	0.9800
1:110226178:GG:G	donor_loss	0.9800
1:110226179:GTATG:G	donor_loss	0.9800
1:110226180:T:C	donor_loss	0.9800
1:110235220:A:T	donor_gain	0.9800
1:110212045:G:GT	donor_gain	0.9700
1:110212079:G:GT	donor_gain	0.9700
1:110222963:GGTA:G	acceptor_gain	0.9700

AlphaMissense

4061 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:110211618:T:A	I40N	1.000
1:110211618:T:C	I40T	1.000
1:110211618:T:G	I40S	1.000
1:110211622:C:A	N41K	1.000
1:110211622:C:G	N41K	1.000
1:110211624:T:A	V42E	1.000
1:110211626:G:C	G43R	1.000
1:110211627:G:A	G43D	1.000
1:110211627:G:T	G43V	1.000
1:110211629:G:C	G44R	1.000
1:110211629:G:T	G44C	1.000
1:110211630:G:A	G44D	1.000
1:110211630:G:T	G44V	1.000
1:110211638:C:G	H47D	1.000
1:110211639:A:C	H47P	1.000
1:110211660:T:A	L54Q	1.000
1:110211660:T:C	L54P	1.000
1:110211678:C:T	T60I	1.000
1:110211684:T:A	L62H	1.000
1:110211684:T:C	L62P	1.000
1:110211782:T:C	F95L	1.000
1:110211784:C:A	F95L	1.000
1:110211784:C:G	F95L	1.000
1:110211789:A:T	D97V	1.000
1:110211792:G:C	R98T	1.000
1:110211792:G:T	R98M	1.000
1:110211793:G:C	R98S	1.000
1:110211793:G:T	R98S	1.000
1:110211795:A:G	H99R	1.000
1:110211806:T:A	F103I	1.000

dbSNP variants (sampled 300 via entrez): RS1000003801 (1:110276112 A>G), RS1000012314 (1:110243275 T>G), RS1000017547 (1:110223664 G>A), RS1000039907 (1:110281434 C>G), RS1000080928 (1:110236384 C>A,T), RS1000103266 (1:110276466 G>A), RS1000134262 (1:110281847 G>A), RS1000156200 (1:110233975 C>T), RS1000173000 (1:110257091 A>G), RS1000223117 (1:110230630 A>C), RS1000314239 (1:110209312 A>G), RS1000428853 (1:110209580 C>A,T), RS1000439969 (1:110233748 G>A), RS1000475150 (1:110267285 T>A), RS1000512452 (1:110220263 C>G)

Disease associations

OMIM: gene MIM:176265 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000747_10	Self-rated health	4.000000e-07
GCST003854_34	Gut microbiota (functional units)	2.000000e-08
GCST003859_5	Oropharynx cancer	1.000000e-06
GCST90002403_13	Red blood cell count	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004778	self rated health
EFO:0007874	gut microbiome measurement
EFO:0004305	erythrocyte count

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
sea anemone toxin BDS-I	Channel blocker	7.3	pIC50
DABCO-C16	Channel blocker	6.2	pIC50
thiopental	Gating inhibitor	4.0	pIC50
tetraethylammonium	Channel blocker	3.5	pIC50
DABCO	Channel blocker	3.2	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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Cisplatin	decreases expression, affects cotreatment, increases expression	2
Valproic Acid	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Bucladesine	affects cotreatment, decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Lead	affects expression	1
Oxygen	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Medroxyprogesterone Acetate	decreases expression, affects cotreatment	1
Reactive Oxygen Species	decreases expression, increases expression, increases oxidation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

21 unique, capped per target: 20 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1787442	Binding	Inhibition of human recombinant Kv channel at 10 uM by radioligand binding assay	Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. — Bioorg Med Chem Lett
CHEMBL5522525	Toxicity	Inhibition of human K+ channel by automated electrophysiology	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem

Clinical trials (associated diseases)

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