KCNK15

Summary

KCNK15 (potassium two pore domain channel subfamily K member 15, HGNC:13814) is a protein-coding gene on chromosome 20q13.12, encoding Potassium channel subfamily K member 15 (Q9H427). Probable potassium channel subunit.

This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel, however, it may require other non-pore-forming proteins for activity.

Source: NCBI Gene 60598 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_022358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13814
Approved symbol	KCNK15
Name	potassium two pore domain channel subfamily K member 15
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	K2p15.1, dJ781B1.1, KT3.3, KIAA0237, TASK5, TASK-5
Ensembl gene	ENSG00000124249
Ensembl biotype	protein_coding
OMIM	607368
Entrez	60598

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372861

RefSeq mRNA: 1 — MANE Select: NM_022358 NM_022358

CCDS: CCDS13337

Canonical transcript exons

ENST00000372861 — 2 exons

Exon	Start	End
ENSE00001458826	44750129	44752313
ENSE00001458827	44745865	44746193

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 86.47.

FANTOM5 (CAGE): breadth broad, TPM avg 5.4070 / max 175.6223, expressed in 551 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184754	4.6132	525
184753	0.6583	231
184752	0.1356	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thoracic aorta	UBERON:0001515	86.47	gold quality
ascending aorta	UBERON:0001496	86.45	gold quality
cerebellar vermis	UBERON:0004720	84.32	gold quality
descending thoracic aorta	UBERON:0002345	83.98	gold quality
left coronary artery	UBERON:0001626	82.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.72	gold quality
right coronary artery	UBERON:0001625	79.35	gold quality
popliteal artery	UBERON:0002250	77.61	gold quality
tibial artery	UBERON:0007610	77.56	gold quality
right uterine tube	UBERON:0001302	73.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.67	silver quality
fallopian tube	UBERON:0003889	72.09	gold quality
omental fat pad	UBERON:0010414	71.04	gold quality
quadriceps femoris	UBERON:0001377	70.51	gold quality
left uterine tube	UBERON:0001303	69.78	gold quality
endocervix	UBERON:0000458	69.26	gold quality
right adrenal gland	UBERON:0001233	68.60	gold quality
body of stomach	UBERON:0001161	68.53	gold quality
adipose tissue	UBERON:0001013	68.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	68.34	gold quality
lower esophagus	UBERON:0013473	68.25	gold quality
adenohypophysis	UBERON:0002196	67.92	gold quality
thymus	UBERON:0002370	67.63	silver quality
left adrenal gland	UBERON:0001234	67.35	gold quality
left adrenal gland cortex	UBERON:0035825	67.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.41	gold quality
subcutaneous adipose tissue	UBERON:0002190	66.35	gold quality
mucosa of stomach	UBERON:0001199	66.29	gold quality
right lobe of thyroid gland	UBERON:0001119	66.02	gold quality
right adrenal gland cortex	UBERON:0035827	65.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43
E-MTAB-7303	no	140.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting KCNK15, 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-1277-5P	100.00	73.95	5056
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-625-5P	99.02	68.64	2031

Literature-anchored findings (GeneRIF, showing 1)

• Potassium channel TASK-5 forms functional heterodimers with TASK-1 and TASK-3 to break its silence. (PMID:39215006)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnk15	ENSDARG00000077371
mus_musculus	Kcnk15	ENSMUSG00000035238
rattus_norvegicus	Kcnk15	ENSRNOG00000010816
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), 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 15 — Q9H427 (reviewed: Q9H427)

Alternative names: Acid-sensitive potassium channel protein TASK-5, TWIK-related acid-sensitive K(+) channel 5, Two pore potassium channel KT3.3

All UniProt accessions (1): Q9H427

UniProt curated annotations — full annotation on UniProt →

Function. Probable potassium channel subunit. No channel activity observed in heterologous systems. May need to associate with another protein to form a functional channel.

Subunit / interactions. Heterodimer.

Subcellular location. Membrane.

Tissue specificity. Detected in pancreas, heart, placenta, lung, liver, kidney, ovary, testis, skeletal muscle and adrenal gland, and at lower levels in prostate, spleen and thyroid gland.

Polymorphism. Three alleles are known: TASK-5A, TASK-5B and TASK-5C. The sequence shown is that of allele TASK-5B.

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

RefSeq proteins (1): NP_071753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003092	2pore_dom_K_chnl_TASK	Family
IPR003280	2pore_dom_K_chnl	Family
IPR008073	TASK5	Family
IPR013099	K_chnl_dom	Domain

Pfam: PF07885

UniProt features (19 total): sequence variant 4, mutagenesis site 4, transmembrane region 4, topological domain 3, intramembrane region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H427-F1	79.31	0.53

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
138	no effect on lack of functional expression.
141–145	no effect on lack of functional expression.
151	no effect on lack of functional expression.
153	no effect on lack of functional expression.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5576886	Phase 4 - resting membrane potential
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction

MSigDB gene sets: 66 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_205, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_RESPONSE_TO_PH, GOBP_CELLULAR_RESPONSE_TO_PH, GOBP_RESPONSE_TO_ACIDIC_PH, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_ABIOTIC_STIMULUS, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOMF_NARROW_PORE_CHANNEL_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_GATED_CHANNEL_ACTIVITY

GO Biological Process (5): cellular response to acidic pH (GO:0071468), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (2): potassium ion leak channel activity (GO:0022841), potassium channel activity (GO:0005267)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cardiac conduction	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to acidic pH	1
cellular response to pH	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
potassium channel activity	1
leak channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNK15	KCNS1	Q96KK3	862
KCNK15	KRT76	Q01546	712
KCNK15	UNC93A	Q86WB7	475
KCNK15	PRKACB	P22694	439
KCNK15	PRKACA	P17612	421
KCNK15	PHAF1	Q9BSU1	413
KCNK15	PRKACG	P22612	408
KCNK15	KCNS2	Q9ULS6	385
KCNK15	KCNK18	Q7Z418	383
KCNK15	ZNF311	Q5JNZ3	371
KCNK15	KCNG4	Q8TDN1	368
KCNK15	TEDC2	Q7L2K0	366
KCNK15	KCNK7	Q9Y2U2	365
KCNK15	DUS4L	O95620	362
KCNK15	KCNU1	A8MYU2	358

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A2Z2U4G9, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, G3V8R8, G5E845, L5KLU7, O00180, O08581, O14649, O17185, O19179, O35111, O35173, O54912, O88758, P26770, P51840, P55203, Q02846, Q0P5A0, Q17ST2, Q1KZG0, Q3LS21, Q3TBV4, Q5RD07, Q5UE96, Q7TNJ2, Q8BH02, Q8IZY2, Q8R454, Q8R5I0

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

60 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

249 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44746144:G:GT	donor_gain	1.0000
20:44746190:ATCGG:A	donor_loss	1.0000
20:44746192:CGGT:C	donor_loss	1.0000
20:44746193:GGTG:G	donor_loss	1.0000
20:44746194:G:GG	donor_gain	1.0000
20:44746194:GTGAG:G	donor_loss	1.0000
20:44746195:T:A	donor_loss	1.0000
20:44750126:T:G	acceptor_gain	1.0000
20:44750127:A:AG	acceptor_gain	1.0000
20:44750128:G:GG	acceptor_gain	1.0000
20:44750128:GA:G	acceptor_gain	1.0000
20:44750128:GAGT:G	acceptor_gain	1.0000
20:44746191:TCG:T	donor_gain	0.9900
20:44749698:T:G	donor_gain	0.9900
20:44750122:T:TA	acceptor_gain	0.9900
20:44750124:CATAG:C	acceptor_gain	0.9900
20:44750125:A:AG	acceptor_gain	0.9900
20:44750125:ATAGA:A	acceptor_gain	0.9900
20:44750128:G:C	acceptor_gain	0.9900
20:44750128:GAGTA:G	acceptor_gain	0.9900
20:44746196:GAGCC:G	donor_loss	0.9800
20:44750124:CATA:C	acceptor_loss	0.9800
20:44750126:TA:T	acceptor_loss	0.9800
20:44750126:TAG:T	acceptor_gain	0.9800
20:44750127:AGA:A	acceptor_gain	0.9800
20:44750128:GAG:G	acceptor_loss	0.9800
20:44749695:T:TA	donor_gain	0.9700
20:44749696:A:AA	donor_gain	0.9700
20:44749727:C:T	donor_gain	0.9700
20:44746144:G:T	donor_gain	0.9500

AlphaMissense

2090 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000068025 (20:44752084 T>C,G), RS1000248497 (20:44746114 G>A), RS1000981711 (20:44745707 C>A,T), RS1001375703 (20:44746632 C>G,T), RS1002054363 (20:44752225 C>A,T), RS1002117612 (20:44751076 T>C), RS1002215229 (20:44746475 G>A), RS1002495097 (20:44747791 G>C), RS1002550685 (20:44748109 T>C), RS1003835669 (20:44748573 G>A), RS1005005905 (20:44751420 C>T), RS1005060027 (20:44751623 G>A), RS1005162604 (20:44745291 C>T), RS1005395034 (20:44752704 A>C,T), RS1005839970 (20:44748662 C>T)

Disease associations

OMIM: gene MIM:607368 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_470	Obesity-related traits	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	3
bisphenol A	increases expression	1
sulforaphane	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
Oxaliplatin	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Dronabinol	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation, increases expression	1
Zearalenone	increases expression	1
Genistein	increases expression	1

Clinical trials (associated diseases)

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