KCNK10

Summary

KCNK10 (potassium two pore domain channel subfamily K member 10, HGNC:6273) is a protein-coding gene on chromosome 14q31.3, encoding Potassium channel subfamily K member 10 (P57789). K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization.

The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 54207 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 79 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_138317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6273
Approved symbol	KCNK10
Name	potassium two pore domain channel subfamily K member 10
Location	14q31.3
Locus type	gene with protein product
Status	Approved
Aliases	K2p10.1, TREK-2, TREK2, PPP1R97
Ensembl gene	ENSG00000100433
Ensembl biotype	protein_coding
OMIM	605873
Entrez	54207

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000312350, ENST00000319231, ENST00000340700, ENST00000556282, ENST00000970839

RefSeq mRNA: 3 — MANE Select: NM_138317 NM_021161, NM_138317, NM_138318

CCDS: CCDS9880, CCDS9881, CCDS9882

Canonical transcript exons

ENST00000319231 — 7 exons

Exon	Start	End
ENSE00000392763	88192224	88192410
ENSE00000808557	88187967	88188109
ENSE00000808558	88227375	88227535
ENSE00000808560	88240703	88240820
ENSE00001171563	88263202	88263551
ENSE00001365826	88322747	88323269
ENSE00003903271	88180108	88186155

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 88.84.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3901 / max 75.5003, expressed in 208 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144406	0.5048	137
144408	0.3040	124
144409	0.2852	124
144407	0.2270	107
144405	0.0691	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	88.84	gold quality
pons	UBERON:0000988	83.96	gold quality
ventricular zone	UBERON:0003053	82.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.01	gold quality
superior vestibular nucleus	UBERON:0007227	81.84	gold quality
ventral tegmental area	UBERON:0002691	80.54	gold quality
medulla oblongata	UBERON:0001896	80.26	gold quality
jejunal mucosa	UBERON:0000399	79.84	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	79.60	silver quality
parietal lobe	UBERON:0001872	77.35	gold quality
inferior olivary complex	UBERON:0002127	76.98	gold quality
gingival epithelium	UBERON:0001949	76.71	silver quality
middle temporal gyrus	UBERON:0002771	76.46	gold quality
entorhinal cortex	UBERON:0002728	76.39	gold quality
postcentral gyrus	UBERON:0002581	76.33	gold quality
gingiva	UBERON:0001828	76.29	gold quality
duodenum	UBERON:0002114	76.25	gold quality
body of tongue	UBERON:0011876	75.96	gold quality
occipital lobe	UBERON:0002021	75.91	gold quality
hair follicle	UBERON:0002073	75.68	silver quality
inferior vagus X ganglion	UBERON:0005363	75.64	gold quality
ganglionic eminence	UBERON:0004023	75.52	gold quality
substantia nigra pars compacta	UBERON:0001965	75.51	silver quality
jejunum	UBERON:0002115	75.41	gold quality
primary visual cortex	UBERON:0002436	75.32	gold quality
cortical plate	UBERON:0005343	75.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.29	gold quality
medial globus pallidus	UBERON:0002477	75.12	gold quality
globus pallidus	UBERON:0001875	75.01	gold quality
esophagus squamous epithelium	UBERON:0006920	74.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

259 targeting KCNK10, 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-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
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-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 14)

• Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. (PMID:11897838)
• Predicts the role of TREK-2 in brain ischemia, memory and other tissues.[REVIEW] (PMID:17689202)
• Tissue-specific mRNA splicing regulates alternative translation initiation (ATI) of human K(2P)10.1 K+ background channels via recombination of 5 nucleotide motifs. (PMID:21669980)
• High TREK-2 expression is associated with epithelial ovarian cancer. (PMID:23479219)
• Modulation of K2P 2.1 and K2P 10.1 K(+) channel sensitivity to carvedilol by alternative mRNA translation initiation (PMID:25168769)
• PLD2, but not PLD1, directly binds to the C terminus of TREK1 and TREK2. (PMID:25197053)
• crystal structures of TREK-2 channel in 2 conformations and in complex with norfluoxetine, a state-dependent blocker of TREK channels; results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli and possible off-target effects of Prozac (PMID:25766236)
• Results suggest that the cytosolic C-terminal domain and the bottom of transmembrane segment M2 are required for the 2-aminoethoxydiphenyl borate activation on TREK-2 channels (PMID:25982558)
• The selectivity filter conformations of alternative translation initiation isoforms and wild type human TREK-2 are similar in the S4 site and pHo position. (PMID:26271386)
• How ion channels sense mechanical force: insights from mechanosensitive K2P channels TRAAK, TREK1, and TREK2. (PMID:26332952)
• This study showed that KCNK10 gene involved in neuronal growth and cerebellum development and associated with neurological and psychological disorders. (PMID:26381449)
• The M2-glycine hinge controls the macroscopic currents of TREK1 channels. (PMID:28676394)
• Effects of ionic strength on gating and permeation of TREK-2 K2P channels. (PMID:34618865)
• beta-COP Suppresses the Surface Expression of the TREK2. (PMID:37296621)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnk10b	ENSDARG00000045956
danio_rerio	kcnk10a	ENSDARG00000062849
mus_musculus	Kcnk10	ENSMUSG00000033854
rattus_norvegicus	Kcnk10	ENSRNOG00000003813
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), KCNK15 (ENSG00000124249), KCNK17 (ENSG00000124780), KCNK1 (ENSG00000135750), KCNK13 (ENSG00000152315), KCNK5 (ENSG00000164626), KCNK9 (ENSG00000169427), KCNK3 (ENSG00000171303), KCNK7 (ENSG00000173338), KCNK4 (ENSG00000182450), KCNK12 (ENSG00000184261), KCNK18 (ENSG00000186795)

Protein

Protein identifiers

Potassium channel subfamily K member 10 — P57789 (reviewed: P57789)

Alternative names: Outward rectifying potassium channel protein TREK-2, TREK-2 K(+) channel subunit

All UniProt accessions (2): P57789, G3V5Y5

UniProt curated annotations — full annotation on UniProt →

Function. K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an ‘ion flux gating’ mode where outward but not inward ion flow opens the gate. Converts to voltage-independent ’leak’ conductance mode upon stimulation by various stimuli including mechanical membrane stretch, acidic pH, heat and lipids. Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. In trigeminal ganglia sensory neurons, the heterodimer of KCNK10/TREK-2 and KCNK18/TRESK inhibits neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency. Permeable to other monovalent ions such as Rb(+) and Cs(+).

Subunit / interactions. Homodimer; disulfide-linked. Forms heterodimers with other 2-pore domain K(+) channel subunits, such as KCNK2, KCNK4 and KCNK18.

Subcellular location. Cell membrane.

Tissue specificity. Abundantly expressed in pancreas and kidney and to a lower level in brain, testis, colon, and small intestine. In brain, mainly expressed in cerebellum, occipital lobe, putamen, and thalamus. No expression is detected in amygdala and spinal cord. Strongly expressed in kidney (primarily in the proximal tubule) and pancreas. Abundantly expressed in brain.

Activity regulation. Activated by various stimuli including acidic pH, anesthetics chloroform, halothane and isoflurane, mechanical stretch, lipids such as arachidonic, docosahexaenoic and linoleic polyunsaturated fatty acids and lysophosphatidylcholine and lysophosphatidylinositol lysophospholipids. Inhibited by norfluoxetine, the active metabolite of antidepressant fluoxetine (Prozac).

Domain organisation. Each subunit contributes two pore-forming domains 1 and 2 which assemble to form a single pore with M2 and M4 transmembrane helices lining the central cavity and M1 and M3 facing the lipid bilayer. The transmembrane helices are bridged by the selectivity filters 1 and 2 carrying a signature sequence TxTTxGYGD 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.

Isoforms (3)

UniProt ID	Names	Canonical?
P57789-1	A, TREK-2a	yes
P57789-4	B, TREK-2b
P57789-3	C, TREK-2c

RefSeq proteins (3): NP_066984, NP_612190, NP_612191 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003280	2pore_dom_K_chnl	Family
IPR003976	2pore_dom_K_chnl_TREK	Family
IPR013099	K_chnl_dom	Domain

Pfam: PF07885

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (65 total): binding site 14, mutagenesis site 11, helix 10, region of interest 4, transmembrane region 4, topological domain 3, glycosylation site 3, strand 3, compositionally biased region 2, intramembrane region 2, splice variant 2, sequence variant 2, chain 1, site 1, disulfide bond 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8QZ3	X-RAY DIFFRACTION	2.4
4BW5	X-RAY DIFFRACTION	3.2
8QZ4	X-RAY DIFFRACTION	3.2
4XDL	X-RAY DIFFRACTION	3.5
8QZ2	X-RAY DIFFRACTION	3.5
8QZ1	X-RAY DIFFRACTION	3.59
4XDK	X-RAY DIFFRACTION	3.6
4XDJ	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57789-F1	69.03	0.29

Antibody-complex structures (SAbDab): 4 — 8QZ1, 8QZ2, 8QZ3, 8QZ4

Functional residue map

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

Catalytic / active sites (1): 151 (ph sensor)

Ligand- & substrate-binding residues (14): 167; 167; 168; 168; 169; 169; 170; 276; 276; 277; 277; 278 …

Disulfide bonds (1): 118

Glycosylation sites (3): 144, 147, 148

Mutagenesis-validated functional residues (11):

Position	Phenotype
98	loss of channel gating by extracellular ph.
151	loss of channel gating by extracellular ph.
174	loss of channel gating by extracellular ph.
210	reduces channel gating by mechanical membrane stretch.
232	reduces channel gating by mechanical membrane stretch.
239	no effect on channel gating by mechanical membrane stretch.
310	near complete loss of channel gating by mechanical membrane stretch.
310	reduces channel gating by mechanical membrane stretch.
315	reduces norfluoxetine inhibition.
317	reduces channel gating by mechanical membrane stretch.
321	reduces channel gating by mechanical membrane stretch.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1299503	TWIK related potassium channel (TREK)
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: 204 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, AP1_01, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_TANDEM_PORE_DOMAIN_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOATOMIC_CATION_TRANSPORT, GTGCCTT_MIR506, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, BLALOCK_ALZHEIMERS_DISEASE_UP, WTGAAAT_UNKNOWN, FOXJ2_01, ATTACAT_MIR3803P

GO Biological Process (6): signal transduction (GO:0007165), potassium ion transmembrane transport (GO:0071805), cellular response to arachidonate (GO:1904551), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (4): potassium channel activity (GO:0005267), outward rectifier potassium channel activity (GO:0015271), potassium ion leak channel activity (GO:0022841), mechanosensitive potassium channel activity (GO:0098782)

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
potassium channel activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
cellular response to fatty acid	1
response to arachidonate	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
leak channel activity	1
mechanosensitive monoatomic cation channel activity	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNK10	KRT76	Q01546	883
KCNK10	KCNK2	O95069	695
KCNK10	PLD2	O14939	647
KCNK10	KCNK18	Q7Z418	569
KCNK10	KCNK9	Q9NPC2	566
KCNK10	KCNK3	O14649	560
KCNK10	PIEZO1	Q92508	549
KCNK10	TMEM14B	Q9NUH8	499
KCNK10	TRPV1	Q8NER1	486
KCNK10	KCNK4	Q9NYG8	475
KCNK10	TRPA1	O75762	464
KCNK10	PIEZO2	Q9H5I5	464
KCNK10	TRPM8	Q7Z2W7	460
KCNK10	KCNA4	P22459	457
KCNK10	KCNJ16	Q9NPI9	455

IntAct

3 interactions, top by confidence:

A	B	Type	Score
KCNK10	KCNK10	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1CA	KCNK10	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): KCNK10 (Affinity Capture-Western)

ESM2 similar proteins: A0A1D5PXA5, A0A1S4GYH6, A1Z7G7, B3MFV7, B3N8M1, B4GD14, B4HS00, B4J780, B4KMZ1, B4LNA8, B4P3A0, G5EFJ9, O01635, O35607, O54852, O73925, P22815, P30432, P34410, P40145, P40146, P48994, P51787, P57789, P79701, P91682, P97414, P97490, Q09274, Q10025, Q13873, Q19187, Q21974, Q24738, Q292N4, Q86GV3, Q95TU8, Q96L42, Q9EPK8, Q9ER47

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1655 predictions. Top by Δscore:

Variant	Effect	Δscore
14:88186151:CCCAC:C	acceptor_gain	1.0000
14:88186152:CCAC:C	acceptor_gain	1.0000
14:88186152:CCACC:C	acceptor_gain	1.0000
14:88186153:CAC:C	acceptor_gain	1.0000
14:88186153:CACC:C	acceptor_gain	1.0000
14:88186154:AC:A	acceptor_gain	1.0000
14:88186155:CC:C	acceptor_gain	1.0000
14:88186156:C:CA	acceptor_loss	1.0000
14:88186161:C:T	acceptor_gain	1.0000
14:88192218:GCTT:G	donor_loss	1.0000
14:88192220:TTACC:T	donor_loss	1.0000
14:88192221:TA:T	donor_loss	1.0000
14:88192222:A:AT	donor_loss	1.0000
14:88192223:C:G	donor_loss	1.0000
14:88192263:C:CT	donor_gain	1.0000
14:88192407:TTTT:T	acceptor_gain	1.0000
14:88192408:TTT:T	acceptor_gain	1.0000
14:88192409:TT:T	acceptor_gain	1.0000
14:88192411:C:CC	acceptor_gain	1.0000
14:88192412:T:G	acceptor_loss	1.0000
14:88192421:C:CT	acceptor_gain	1.0000
14:88192422:A:T	acceptor_gain	1.0000
14:88227367:GTACT:G	donor_loss	1.0000
14:88227368:TAC:T	donor_loss	1.0000
14:88227369:ACTC:A	donor_loss	1.0000
14:88227370:CTC:C	donor_loss	1.0000
14:88227371:T:TA	donor_loss	1.0000
14:88227372:CA:C	donor_loss	1.0000
14:88227373:A:AC	donor_gain	1.0000
14:88227373:AC:A	donor_loss	1.0000

AlphaMissense

3559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:88186123:C:A	W343C	1.000
14:88186123:C:G	W343C	1.000
14:88186125:A:G	W343R	1.000
14:88186125:A:T	W343R	1.000
14:88188040:A:G	L308P	1.000
14:88188044:C:G	G307R	1.000
14:88188056:A:G	W303R	1.000
14:88188056:A:T	W303R	1.000
14:88227445:A:G	L199S	1.000
14:88227454:C:T	G196D	1.000
14:88227463:G:T	P193Q	1.000
14:88227469:C:T	G191E	1.000
14:88227470:C:G	G191R	1.000
14:88227470:C:T	G191R	1.000
14:88227529:C:T	G171E	1.000
14:88240752:C:A	W152C	1.000
14:88240752:C:G	W152C	1.000
14:88240754:A:G	W152R	1.000
14:88240754:A:T	W152R	1.000
14:88263254:A:G	F112S	1.000
14:88263332:C:T	G86D	1.000
14:88263341:A:G	L83P	1.000
14:88186085:C:G	R356P	0.999
14:88186107:C:G	A349P	0.999
14:88186119:C:G	A345P	0.999
14:88188019:A:G	L315P	0.999
14:88188019:A:T	L315H	0.999
14:88188025:G:T	A313D	0.999
14:88188026:C:G	A313P	0.999
14:88188028:G:T	A312E	0.999

dbSNP variants (sampled 300 via entrez): RS1000033885 (14:88250861 A>G), RS1000047394 (14:88208760 C>G), RS1000108677 (14:88249007 C>T), RS1000111805 (14:88268578 G>A), RS1000114025 (14:88309313 T>C), RS1000115714 (14:88283532 G>A,T), RS1000148143 (14:88255049 C>A,T), RS1000157671 (14:88253190 C>A,T), RS1000190625 (14:88211940 T>C), RS1000193239 (14:88292778 A>G), RS1000193556 (14:88282195 G>A), RS1000203413 (14:88281810 T>C), RS1000219104 (14:88284163 T>C), RS1000220898 (14:88202963 G>C), RS1000230686 (14:88252841 G>C)

Disease associations

OMIM: gene MIM:605873 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002518_7	Food antigen IgG levels	4.000000e-07
GCST004485_33	Survival in pancreatic cancer	9.000000e-06
GCST006575_6	Takayasu arteritis	6.000000e-06
GCST007001_8	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07
GCST010242_66	HDL cholesterol levels	4.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005844	response to dietary antigen
EFO:0000638	overall survival
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2331041 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 30,225 (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
CHEMBL723	CARVEDILOL	4	30,225

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 (6 total), top 6:

Ligand	Action	Affinity	Parameter
Nb-Activator-67	Activation	7.0	pEC50
ONO-TR-772	Inhibition	6.77	pIC50
ONO-2920632	Activation	6.52	pEC50
Nb-Activator-76	Activation	6.39	pEC50
Nb-Inhibitor-61	Inhibition	6.16	pIC50
BL-1249	Activator	5.1	pEC50

ChEMBL bioactivities

9 potent at pChembl≥5 of 16 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.30	EC50	5000	nM	CHEMBL4745050
5.26	EC50	5500	nM	CHEMBL4759521
5.25	EC50	5600	nM	CHEMBL4795261
5.23	EC50	5900	nM	CHEMBL4747631
5.17	EC50	6800	nM	CHEMBL4776102
5.12	IC50	7600	nM	CARVEDILOL
5.12	EC50	7500	nM	CHEMBL4780579
5.11	EC50	7700	nM	CHEMBL1417584
5.11	EC50	7700	nM	CHEMBL4759642

PubChem BioAssay actives

10 with measured affinity, of 71 total; 10 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
4,5-dimethyl-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]thiophene-3-carboxylic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	3.6000	uM
2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	5.0000	uM
5-bromo-4-fluoro-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	5.5000	uM
5-(trifluoromethoxy)-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	5.6000	uM
4-bromo-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	5.9000	uM
5-chloro-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	6.8000	uM
4-chloro-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	7.5000	uM
Carvedilol	1307736: Inhibition of of TREK2 (unknown origin) expressed in HEK293 cells assessed as reduction in channel currents	ic50	7.6000	uM
N-[2-(2H-tetrazol-5-yl)phenyl]-5,6,7,8-tetrahydronaphthalen-1-amine	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	7.7000	uM
5-bromo-2-[[4-(trifluoromethylsulfanyl)benzoyl]amino]benzoic acid	1672907: Activation of human TREK2 by thallium flux mobilization assay	ec50	7.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	affects acetylation, affects methylation, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	increases methylation	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	affects acetylation, affects methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Diltiazem	decreases reaction, increases transport	1
Flufenamic Acid	increases reaction, increases transport	1
Halothane	increases transport, increases reaction	1
Mefenamic Acid	increases reaction, increases transport	1
Niflumic Acid	increases reaction, increases transport	1
Potassium	increases reaction, increases transport, decreases reaction	1
Rotenone	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3819943	Binding	Activation of TREK2 (unknown origin) expressed in Xenopus oocytes assessed as increase in channel currents	Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target? — J Med Chem

Clinical trials (associated diseases)

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