KCNK13

Summary

KCNK13 (potassium two pore domain channel subfamily K member 13, HGNC:6275) is a protein-coding gene on chromosome 14q32.11, encoding Potassium channel subfamily K member 13 (Q9HB14). K(+) channel that conducts outward rectifying tonic currents potentiated by purinergic signals.

Potassium 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 potassium channel containing two pore-forming domains. This protein is an open channel that can be stimulated by arachidonic acid and inhibited by the anesthetic halothane.

Source: NCBI Gene 56659 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 63 total
• Druggable target: yes
• MANE Select transcript: NM_022054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6275
Approved symbol	KCNK13
Name	potassium two pore domain channel subfamily K member 13
Location	14q32.11
Locus type	gene with protein product
Status	Approved
Aliases	K2p13.1, THIK-1, THIK1
Ensembl gene	ENSG00000152315
Ensembl biotype	protein_coding
OMIM	607367
Entrez	56659

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000282146, ENST00000954166

RefSeq mRNA: 1 — MANE Select: NM_022054 NM_022054

CCDS: CCDS9889

Canonical transcript exons

ENST00000282146 — 2 exons

Exon	Start	End
ENSE00001004646	90184111	90185853
ENSE00001216619	90061994	90062539

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 75.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1876 / max 18.9246, expressed in 103 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141002	0.1876	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	75.49	gold quality
left testis	UBERON:0004533	74.20	gold quality
monocyte	CL:0000576	72.03	gold quality
testis	UBERON:0000473	71.85	gold quality
leukocyte	CL:0000738	71.72	gold quality
granulocyte	CL:0000094	66.07	gold quality
vermiform appendix	UBERON:0001154	64.91	gold quality
metanephros cortex	UBERON:0010533	64.53	gold quality
adult mammalian kidney	UBERON:0000082	63.36	gold quality
right atrium auricular region	UBERON:0006631	62.59	gold quality
cardiac atrium	UBERON:0002081	62.02	gold quality
left lobe of thyroid gland	UBERON:0001120	60.83	gold quality
prefrontal cortex	UBERON:0000451	60.20	gold quality
right lobe of thyroid gland	UBERON:0001119	60.19	gold quality
thyroid gland	UBERON:0002046	59.64	gold quality
caecum	UBERON:0001153	59.54	gold quality
anterior cingulate cortex	UBERON:0009835	58.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.29	gold quality
metanephros	UBERON:0000081	57.38	gold quality
apex of heart	UBERON:0002098	57.18	gold quality
hypothalamus	UBERON:0001898	56.79	gold quality
spinal cord	UBERON:0002240	56.64	gold quality
endometrium	UBERON:0001295	55.98	gold quality
cortex of kidney	UBERON:0001225	55.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	55.57	gold quality
heart	UBERON:0000948	55.45	gold quality
kidney	UBERON:0002113	55.45	gold quality
blood	UBERON:0000178	54.93	gold quality
amygdala	UBERON:0001876	54.88	gold quality
heart left ventricle	UBERON:0002084	54.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	51.25
E-ANND-3	no	1.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting KCNK13, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 5)

• expression in cell hypoxia (PMID:16683720)
• THIK-1 and THIK-2 are abundantly expressed in the proximal and distal nephron of the mammalian kidney. (PMID:18209473)
• In cell and tissues co-expressing THIK1 and THIK2, heterodimeric channels may contribute to cell excitability. (PMID:25148687)
• Dysregulation of a potassium channel, THIK-1, targeted by caspase-8, accelerates cell shrinkage. (PMID:27566292)
• Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors. (PMID:37099539)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnk13a	ENSDARG00000008212
danio_rerio	kcnk13b	ENSDARG00000043557
mus_musculus	Kcnk13	ENSMUSG00000045404
rattus_norvegicus	Kcnk13	ENSRNOG00000047363
drosophila_melanogaster	Ork1	FBGN0017561
drosophila_melanogaster	Task7	FBGN0037690
drosophila_melanogaster	Task6	FBGN0038165
drosophila_melanogaster	CG10864	FBGN0038621
drosophila_melanogaster	CG42340	FBGN0259242
caenorhabditis_elegans		WBGENE00006661
caenorhabditis_elegans		WBGENE00006674
caenorhabditis_elegans		WBGENE00006675
caenorhabditis_elegans		WBGENE00006679
caenorhabditis_elegans		WBGENE00006685
caenorhabditis_elegans		WBGENE00006686
caenorhabditis_elegans		WBGENE00006695
caenorhabditis_elegans		WBGENE00006696

Paralogs (14): KCNK2 (ENSG00000082482), KCNK16 (ENSG00000095981), KCNK6 (ENSG00000099337), KCNK10 (ENSG00000100433), KCNK15 (ENSG00000124249), KCNK17 (ENSG00000124780), KCNK1 (ENSG00000135750), KCNK5 (ENSG00000164626), KCNK9 (ENSG00000169427), KCNK3 (ENSG00000171303), KCNK7 (ENSG00000173338), KCNK4 (ENSG00000182450), KCNK12 (ENSG00000184261), KCNK18 (ENSG00000186795)

Protein

Protein identifiers

Potassium channel subfamily K member 13 — Q9HB14 (reviewed: Q9HB14)

Alternative names: Tandem pore domain halothane-inhibited potassium channel 1

All UniProt accessions (1): Q9HB14

UniProt curated annotations — full annotation on UniProt →

Function. K(+) channel that conducts outward rectifying tonic currents potentiated by purinergic signals. Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. Contributes most of K(+) currents at the plasma membrane of resting microglia. Maintains a depolarized membrane potential required for proper ramified microglia morphology and phagocytosis, selectively mediating microglial pruning of presynaptic compartments at hippocampal excitatory synapses. Upon local release of ATP caused by neuronal injury or infection, it is potentiated by P2RY12 and P2RX7 receptor signaling and contributes to ATP-triggered K(+) efflux underlying microglial NLRP3 inflammasome assembly and IL1B release.

Subunit / interactions. Homodimer. Heterodimer with KCNK12.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in microglia (at protein level).

Activity regulation. Activated by anionic lipids such as phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2 or PIP2) and oleoyl-CoA. Activated by arachidonic acid. Inhibited by channel blocker tetrapentylammonium. Inhibited by Ba(2+) ions, volatile anesthetics such as halothane and isoflurane, and antiarrhythmic drugs mexiletine and lidocaine. Insensitive to extracellular pH change.

Domain organisation. Each subunit contributes two pore-forming domains which assemble to form a single pore. The transmembrane helices are bridged by the selectivity filters 1 and 2 that coordinate the permeant ions. Up to four ions can simultaneously occupy the selectivity filter and at least two elementary charges must translocate across the filter to convert it into the open conformation.

Similarity. Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.

RefSeq proteins (1): NP_071337* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003280	2pore_dom_K_chnl	Family
IPR005410	2pore_dom_K_chnl_THIK	Family
IPR013099	K_chnl_dom	Domain

Pfam: PF07885

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (50 total): binding site 14, mutagenesis site 7, helix 7, topological domain 5, transmembrane region 4, strand 3, region of interest 2, glycosylation site 2, sequence variant 2, turn 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
9C09	ELECTRON MICROSCOPY	2.36
9BWS	ELECTRON MICROSCOPY	2.39
9M9M	ELECTRON MICROSCOPY	2.52
9BSN	ELECTRON MICROSCOPY	2.7
9C07	ELECTRON MICROSCOPY	2.73
9JGZ	ELECTRON MICROSCOPY	2.74
9M9X	ELECTRON MICROSCOPY	2.76
9M9W	ELECTRON MICROSCOPY	2.87
9M9Q	ELECTRON MICROSCOPY	2.92
9BYI	ELECTRON MICROSCOPY	2.95
9JH1	ELECTRON MICROSCOPY	3.07
9FT7	ELECTRON MICROSCOPY	3.16
9DWN	ELECTRON MICROSCOPY	3.2
9U8B	ELECTRON MICROSCOPY	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HB14-F1	74.74	0.39

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 (14): 110; 110; 111; 111; 112; 112; 113; 237; 237; 238; 238; 239 …

Glycosylation sites (2): 59, 65

Mutagenesis-validated functional residues (7):

Position	Phenotype
87	decreases channel basal activity.
112	acts as a dominant negative when it assembles with wild-type kcnk13 or kcnk12 subunits, abolishing k(+) flux.
136	increases channel basal activity. increases the current amplitude. confers nonlinear i-v relationship, with currents tha
139	increases channel basal activity.
139	increases channel basal activity. increases the current amplitude. confers nonlinear i-v relationship, with currents tha
261	decreases channel basal activity.
273	increases channel basal activity.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1299287	Tandem pore domain halothane-inhibited K+ channel (THIK)
R-HSA-5576886	Phase 4 - resting membrane potential
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels
R-HSA-1296346	Tandem pore domain potassium channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 176 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, PAX4_01, GOBP_INFLAMMATORY_RESPONSE, REACTOME_TANDEM_PORE_DOMAIN_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY

GO Biological Process (7): regulation of resting membrane potential (GO:0060075), potassium ion transmembrane transport (GO:0071805), regulation of NLRP3 inflammasome complex assembly (GO:1900225), regulation of excitatory synapse pruning (GO:1905810), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (7): potassium channel activity (GO:0005267), outward rectifier potassium channel activity (GO:0015271), potassium ion leak channel activity (GO:0022841), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Tandem pore domain potassium channels	1
Cardiac conduction	1
Neuronal System	1
Potassium Channels	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of membrane potential	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
regulation of inflammasome-mediated signaling pathway	1
excitatory synapse pruning	1
regulation of synapse pruning	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
voltage-gated potassium channel activity	1
potassium channel activity	1
leak channel activity	1
protein binding	1
cation binding	1
protein dimerization activity	1
binding	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNK13	KCNK18	Q7Z418	756
KCNK13	KCNK12	Q9HB15	719
KCNK13	KRT76	Q01546	716
KCNK13	KCNK6	Q9Y257	536
KCNK13	KCNG1	Q9UIX4	526
KCNK13	KCNAB3	O43448	506
KCNK13	P2RY12	Q9H244	479
KCNK13	KCNK4	Q9NYG8	462
KCNK13	PRKACB	P22694	445
KCNK13	KCNK7	Q9Y2U2	439
KCNK13	PRKACG	P22612	436
KCNK13	PRKACA	P17612	434
KCNK13	KCNMA1	Q12791	395
KCNK13	KCNG3	Q8TAE7	391
KCNK13	KCNU1	A8MYU2	383

IntAct

4 interactions, top by confidence:

A	B	Type	Score
KCNK13	KCNK13	psi-mi:“MI:2364”(proximity)	0.350
KCNK13	KCNK12	psi-mi:“MI:2364”(proximity)	0.350
KCNK12	KCNK13	psi-mi:“MI:2364”(proximity)	0.350

BioGRID (2): KCNK13 (Two-hybrid), KCNK13 (Positive Genetic)

ESM2 similar proteins: A2BDX4, A4K2T1, A4K2Y2, D4AD53, O15554, O73606, O88454, O89109, P15388, P17971, P17972, P35739, P48547, P59053, P59994, P59995, P97557, Q03719, Q0P583, Q17ST2, Q52PG9, Q5RC10, Q60565, Q63881, Q6IVV8, Q6PIU1, Q7TN37, Q80XM3, Q8BZN2, Q8CFS6, Q8HYZ1, Q8IV77, Q8R1P5, Q8R523, Q8TAE7, Q8TD43, Q8TDN1, Q8TDN2, Q96RP8, Q9ERS0

Diamond homologs: G3V8R8, G3V8V5, G5E845, O00180, O08581, O14649, O17185, O35111, O54912, O88454, O95069, O95279, P57789, P97438, Q0P5A0, Q23435, Q3LS21, Q3TBV4, Q5RD07, Q5UE96, Q5VSE6, Q63ZI0, Q6Q1P3, Q6VV64, Q7Z418, Q8BUW1, Q8R454, Q8R5I0, Q920B6, Q96T54, Q96T55, Q9ERS1, Q9ES08, Q9H427, Q9HB14, Q9HB15, Q9JIS4, Q9JL58, Q9NPC2, Q9NYG8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1068 predictions. Top by Δscore:

Variant	Effect	Δscore
14:90062536:ATAGG:A	donor_loss	1.0000
14:90062537:TAGG:T	donor_loss	1.0000
14:90062538:AGGTA:A	donor_loss	1.0000
14:90062539:GGTA:G	donor_loss	1.0000
14:90062540:G:GA	donor_loss	1.0000
14:90062540:G:GG	donor_gain	1.0000
14:90062541:T:A	donor_loss	1.0000
14:90062535:CATAG:C	donor_gain	0.9900
14:90062536:ATAG:A	donor_gain	0.9900
14:90062537:TAG:T	donor_gain	0.9900
14:90062538:AG:A	donor_gain	0.9900
14:90062539:GG:G	donor_gain	0.9900
14:90184106:T:A	acceptor_gain	0.9900
14:90184106:TGCAG:T	acceptor_loss	0.9900
14:90184107:GCAGG:G	acceptor_loss	0.9900
14:90184109:A:AG	acceptor_gain	0.9900
14:90184109:AG:A	acceptor_gain	0.9900
14:90184109:AGG:A	acceptor_gain	0.9900
14:90184110:G:GA	acceptor_gain	0.9900
14:90184110:GG:G	acceptor_gain	0.9900
14:90184110:GGG:G	acceptor_gain	0.9900
14:90184110:GGGT:G	acceptor_gain	0.9900
14:90184110:GGGTT:G	acceptor_gain	0.9900
14:90107870:G:GT	donor_gain	0.9800
14:90107883:GGCCT:G	donor_gain	0.9800
14:90107884:GCCT:G	donor_gain	0.9800
14:90108649:T:G	donor_gain	0.9800
14:90136178:G:GT	donor_gain	0.9800
14:90095746:G:GT	donor_gain	0.9700
14:90095810:TC:T	donor_gain	0.9700

AlphaMissense

2678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:90062488:T:A	W95R	0.998
14:90062488:T:C	W95R	0.998
14:90062490:G:C	W95C	0.998
14:90062490:G:T	W95C	0.998
14:90184113:T:C	F113L	0.998
14:90184115:T:A	F113L	0.998
14:90184115:T:G	F113L	0.998
14:90184482:A:C	S236R	0.998
14:90184484:C:A	S236R	0.998
14:90184484:C:G	S236R	0.998
14:90184111:G:A	G112E	0.997
14:90184498:G:A	G241E	0.997
14:90184498:G:T	G241V	0.997
14:90184117:G:A	G114E	0.996
14:90184464:T:C	F230L	0.996
14:90184466:C:A	F230L	0.996
14:90184466:C:G	F230L	0.996
14:90184494:T:C	F240L	0.996
14:90184496:T:A	F240L	0.996
14:90184496:T:G	F240L	0.996
14:90184497:G:T	G241W	0.996
14:90184509:A:C	S245R	0.996
14:90184511:C:A	S245R	0.996
14:90184511:C:G	S245R	0.996
14:90184578:G:C	G268R	0.996
14:90062317:T:C	F38L	0.995
14:90062319:C:A	F38L	0.995
14:90062319:C:G	F38L	0.995
14:90062512:T:C	F103L	0.995
14:90062514:C:A	F103L	0.995

dbSNP variants (sampled 300 via entrez): RS1000000373 (14:90169672 C>A,T), RS1000061534 (14:90126933 A>G), RS1000069979 (14:90143909 C>G,T), RS1000113598 (14:90127291 C>T), RS1000125735 (14:90151816 G>A), RS1000131874 (14:90086306 C>T), RS1000148630 (14:90071540 T>C), RS1000175255 (14:90064992 G>T), RS1000182763 (14:90178760 C>G), RS1000187592 (14:90167489 G>T), RS1000233922 (14:90079658 A>G), RS1000270055 (14:90064661 C>T), RS1000277396 (14:90106656 CTATA>C), RS1000298640 (14:90121750 C>G,T), RS1000355155 (14:90115238 G>A)

Disease associations

OMIM: gene MIM:607367 | disease phenotypes: MIM:200600

GenCC curated gene-disease

Mondo (1): achondrogenesis type IA (MONDO:0008701)

Orphanet (2): Achondrogenesis (Orphanet:932), Achondrogenesis type 1A (Orphanet:93299)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000661_5	Mortality in heart failure	7.000000e-06
GCST002097_48	Coronary artery calcification	4.000000e-06
GCST006675_1	Peak insulin response (BMI and insulin secretion adjusted)	4.000000e-08
GCST007102_6	Seasonality and depression	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0004723	coronary artery calcification
EFO:0008000	peak insulin response measurement
EFO:0006876	seasonality measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536015	Achondrogenesis type 1A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523461 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Two-pore domain potassium channels (K_2P)

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

Ligand	Action	Affinity	Parameter
CVN293	Inhibition	7.31	pIC50

ChEMBL bioactivities

20 potent at pChembl≥5 of 20 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.47	IC50	34	nM	CHEMBL5646788
7.43	IC50	37	nM	CHEMBL5639376
7.39	IC50	41	nM	CHEMBL5646860
7.38	IC50	42	nM	CHEMBL5646481
7.34	IC50	46	nM	CHEMBL3422154
7.34	IC50	46	nM	CHEMBL5641517
7.34	IC50	46	nM	CHEMBL5641707
7.33	IC50	47	nM	CHEMBL5639774
7.31	IC50	49	nM	CHEMBL5641684
7.30	IC50	50	nM	CHEMBL5639899
7.30	IC50	50	nM	CHEMBL5647460
7.30	IC50	50	nM	CHEMBL5639527
7.26	IC50	55	nM	CHEMBL5647519
7.08	IC50	84	nM	CHEMBL5639178
7.05	IC50	89	nM	CHEMBL5639821
5.53	IC50	2940	nM	CHEMBL5647313
5.46	IC50	3430	nM	CHEMBL5647133
5.04	IC50	9200	nM	CHEMBL5646908

PubChem BioAssay actives

20 with measured affinity, of 25 total; 18 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
4-[6-fluoro-1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0340	uM
4-[4,7-difluoro-1-(pyridazin-3-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0370	uM
4-[7-fluoro-1-(pyridazin-3-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0410	uM
4-[5-fluoro-1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0420	uM
4-[7-fluoro-1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0460	uM
4-[7-fluoro-1-(pyrimidin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0460	uM
4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144428: Inhibition of human KCNK13 transfected in HEK293 cells by QPatch assay	ic50	0.0460	uM
4-[7-fluoro-1-(pyrazin-2-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0470	uM
4-[7-fluoro-1-(pyrimidin-5-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0490	uM
4-[7-fluoro-1-(pyridazin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0500	uM
4-[6,7-difluoro-1-(pyridazin-3-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0500	uM
6-[[2-(4-amino-1,2,5-oxadiazol-3-yl)-7-fluorobenzimidazol-1-yl]methyl]pyridazine-3-carbonitrile	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0500	uM
4-[4-fluoro-1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0550	uM
4-[7-fluoro-1-[[6-(trifluoromethyl)pyridazin-3-yl]methyl]benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0840	uM
3-methyl-4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazole	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	0.0890	uM
4-[1-(pyridin-4-ylmethyl)benzimidazol-2-yl]-1,3-oxazole	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	2.9400	uM
2-(1H-imidazol-2-yl)-1-(pyridin-4-ylmethyl)benzimidazole	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	3.4300	uM
2-(1H-pyrazol-5-yl)-1-(pyridin-4-ylmethyl)benzimidazole	2144431: Inhibition of human KCNK13 transfected in HEK293 cells	ic50	9.2000	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, decreases methylation	2
Fenofibrate	increases expression	2
methyleugenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Niclosamide	decreases expression	1
Triclosan	decreases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4359055	Binding	Activation of recombinant human THIK1 expressed in HEK293T cells assessed as increase in K+ current amplitude at 10 uM by whole cell voltage clamp electrophysiological analysis	TREK Channel Family Activator with a Well-Defined Structure-Activation Relationship for Pain and Neurogenic Inflammation. — J Med Chem

Clinical trials (associated diseases)

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