KCNK5

Summary

KCNK5 (potassium two pore domain channel subfamily K member 5, HGNC:6280) is a protein-coding gene on chromosome 6p21.2, encoding Potassium channel subfamily K member 5 (O95279). K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization.

This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport.

Source: NCBI Gene 8645 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 68 total
• Druggable target: yes
• MANE Select transcript: NM_003740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6280
Approved symbol	KCNK5
Name	potassium two pore domain channel subfamily K member 5
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	K2p5.1, TASK-2, TASK2
Ensembl gene	ENSG00000164626
Ensembl biotype	protein_coding
OMIM	603493
Entrez	8645

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000359534, ENST00000907345, ENST00000927503

RefSeq mRNA: 1 — MANE Select: NM_003740 NM_003740

CCDS: CCDS4841

Canonical transcript exons

ENST00000359534 — 5 exons

Exon	Start	End
ENSE00001086064	39194169	39194337
ENSE00001086066	39194594	39194760
ENSE00001086067	39195876	39195987
ENSE00001410945	39188971	39191755
ENSE00001418591	39228926	39229475

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 95.39.

FANTOM5 (CAGE): breadth broad, TPM avg 6.5833 / max 171.3050, expressed in 703 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73473	6.5833	703

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	95.39	silver quality
mucosa of transverse colon	UBERON:0004991	89.79	gold quality
ileal mucosa	UBERON:0000331	89.10	gold quality
oocyte	CL:0000023	87.89	gold quality
duodenum	UBERON:0002114	87.86	gold quality
adult mammalian kidney	UBERON:0000082	87.56	gold quality
nephron tubule	UBERON:0001231	87.08	gold quality
secondary oocyte	CL:0000655	86.66	gold quality
jejunal mucosa	UBERON:0000399	86.07	gold quality
skin of leg	UBERON:0001511	85.84	gold quality
gall bladder	UBERON:0002110	85.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.57	gold quality
small intestine	UBERON:0002108	85.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.95	gold quality
right lobe of liver	UBERON:0001114	84.82	gold quality
tibia	UBERON:0000979	84.81	gold quality
minor salivary gland	UBERON:0001830	84.79	gold quality
cervix squamous epithelium	UBERON:0006922	84.70	gold quality
kidney epithelium	UBERON:0004819	84.10	gold quality
kidney	UBERON:0002113	83.93	gold quality
saliva-secreting gland	UBERON:0001044	83.85	gold quality
body of pancreas	UBERON:0001150	83.81	gold quality
cartilage tissue	UBERON:0002418	83.73	gold quality
metanephros cortex	UBERON:0010533	83.60	gold quality
adrenal tissue	UBERON:0018303	82.92	gold quality
transverse colon	UBERON:0001157	82.79	gold quality
zone of skin	UBERON:0000014	82.74	gold quality
mouth mucosa	UBERON:0003729	82.66	gold quality
nasal cavity epithelium	UBERON:0005384	82.19	gold quality
skin of abdomen	UBERON:0001416	82.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, NR1I2

miRNA regulators (miRDB)

67 targeting KCNK5, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-302A-5P	99.39	68.21	1913

Literature-anchored findings (GeneRIF, showing 19)

• TASK-2 does not possess a histidine residue at homologous position. Inclusion of such a residue failed to produce expected increase in pH sensitivity; instead, a slight decrease was observed (PMID:12634929)
• TASK-2 is not highly expressed in cerebellum (PMID:15197476)
• KCNK5 is involved K(+)-channel in regulatory volume decrease in human spermatozoa, and channel activity is regulated beyond the extent of protein expression. (PMID:18157847)
• We here identify and characterize K2P5.1 as a critical player of T-cell effector function; selective targeting of K(2P)5.1 may hold therapeutic promise for multiple sclerosis and putatively other T-cell-mediated disorders. (PMID:20582984)
• Data suggest that the cytokine receptor-coupled JAK/STAT pathway is upstream of the swelling-induced phosphorylation and activation of TASK-2 in Ehrlich ascites tumor cells. (PMID:20631251)
• Disease activity in rheumatoid arthritis patients correlates strongly with K(2P)5.1 expression levels in CD4+ T lymphocytes in the peripheral blood (PMID:21314928)
• 17beta-estradiol induces the expression of KCNK5 via ERalpha(+) in breast cancer cells, and this channel plays a role in regulating proliferation in these cell lines. (PMID:21680658)
• Potassium channels, in particular K2P channels, are expressed and functional in the apical membrane of airway epithelial cells (PMID:21964404)
• The TASK-2 channel lower expression represents a hallmark of aldosterone-producing adenoma causing aldosteronism and is associated with a higher expression of hsa-miR-23 and hsa-miR-34. (PMID:24285684)
• Mutant genes (CELA1, HSPG2, and KCNK5) in Balkan endemic nephropathy patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. (PMID:24949484)
• Potassium channel TASK2 drives human NK-cell proliferation and cytolytic function. (PMID:26140335)
• Results show that up-regulated KCNK5 in activated human T cells does not play a volume regulatory role, due to decreased Cl- permeability suggesting that the KCNK5 upregulation might play a role in hyperpolarization of the cell membrane leading to increased Ca2+ influx and proliferation of T cells. (PMID:26909737)
• These results therefore provide further structural and functional insights into the possible pathophysiological effects of this missense variant in TASK-2. (PMID:27228168)
• HLA-DQB1*06:02 does not seem to be associated with hypoxic ventilatory response or hypercapnic ventilatory response; however there are point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and hypercapnic ventilatory response (PMID:28045995)
• In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. (PMID:28604387)
• As a novel finding, our study suggests a role for KCNK5 in the regulation of platelet size and maturity. Furthermore, our findings confirm an association between the SH2B3-locus and platelet count. (PMID:28865245)
• mutations in the promoter region of the TWIK-related acid-sensitive K(+) channel 2 (TASK-2) gene did not result in hypertension or primary aldosteronism (PA) during long-term follow-up in healthy participants thus they do not seem to be a factor in causing PA by themselves. (PMID:29293917)
• Common variants in KCNK5 and FHL5 genes contributed to the susceptibility of migraine without aura in Han Chinese population. (PMID:33762637)
• KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye. (PMID:38236186)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnk5b	ENSDARG00000012390
danio_rerio	kcnk5a	ENSDARG00000023587
mus_musculus	Kcnk5	ENSMUSG00000023243
rattus_norvegicus	Kcnk5	ENSRNOG00000047005
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), KCNK13 (ENSG00000152315), KCNK9 (ENSG00000169427), KCNK3 (ENSG00000171303), KCNK7 (ENSG00000173338), KCNK4 (ENSG00000182450), KCNK12 (ENSG00000184261), KCNK18 (ENSG00000186795)

Protein

Protein identifiers

Potassium channel subfamily K member 5 — O95279 (reviewed: O95279)

Alternative names: Acid-sensitive potassium channel protein TASK-2, TWIK-related acid-sensitive K(+) channel 2

All UniProt accessions (1): O95279

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. Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with KCNK16 and KCNK17.

Subcellular location. Membrane.

Tissue specificity. Abundant expression in kidney, also detected in liver, placenta and small intestine. In the kidney, expression is restricted to the distal tubules and collecting ducts. Not expressed in proximal tubules or glomeruli. Expressed in pancreas, in both endocrine (alpha, beta, gamma, delta, and epsilon) and exocrine (acinar and ductal) cells.

Activity regulation. The channel conductance is stimulated by extracellular alkaline pH. Inhibited by quinine, quinidine and external acidification.

Domain organisation. The pore-forming domains 1 and 2 assemble to form a single pore in which M2 and M4 transmembrane helices line the central cavity and M1 and M3 face 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.

RefSeq proteins (1): NP_003731* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF07885

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (39 total): binding site 14, region of interest 5, transmembrane region 4, topological domain 3, compositionally biased region 3, intramembrane region 2, mutagenesis site 2, chain 1, modified residue 1, glycosylation site 1, disulfide bond 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95279-F1	69.94	0.34

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): 98; 98; 99; 99; 100; 100; 101; 203; 203; 204; 204; 205 …

Post-translational modifications (1): 371

Disulfide bonds (1): 51

Glycosylation sites (1): 77

Mutagenesis-validated functional residues (2):

Position	Phenotype
98	abolishes voltage-dependent gating. conducts instantaneous currents with linear current-voltage relationship.
203	abolishes voltage-dependent gating. conducts instantaneous currents with linear current-voltage relationship.

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: 215 (showing top): VALK_AML_WITH_FLT3_ITD, GOBP_POTASSIUM_ION_TRANSPORT, TGCGCANK_UNKNOWN, TGACCTY_ERR1_Q2, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BLALOCK_ALZHEIMERS_DISEASE_UP, GATA6_01, SMID_BREAST_CANCER_RELAPSE_IN_BRAIN_UP, BROWN_MYELOID_CELL_DEVELOPMENT_DN

GO Biological Process (7): potassium ion transport (GO:0006813), regulation of resting membrane potential (GO:0060075), potassium ion transmembrane transport (GO:0071805), potassium ion export across plasma membrane (GO:0097623), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), 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), metal ion binding (GO:0046872), protein heterodimerization activity (GO:0046982), voltage-gated potassium channel activity (GO:0005249), 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-2 pathways:

Category	Pathways
Cardiac conduction	1
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
potassium ion transmembrane transport	2
potassium channel activity	2
metal ion transport	1
regulation of membrane potential	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
export across plasma membrane	1
inorganic cation import across plasma membrane	1
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
cation binding	1
protein dimerization activity	1
voltage-gated monoatomic cation channel activity	1
binding	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNK5	KRT76	Q01546	799
KCNK5	KCNK3	O14649	626
KCNK5	KCNK9	Q9NPC2	618
KCNK5	GPR4	P46093	577
KCNK5	KCNJ4	P48050	572
KCNK5	KCNN4	O15554	561
KCNK5	KCNA3	P22001	497
KCNK5	KCNJ16	Q9NPI9	497
KCNK5	PHOX2B	Q99453	490
KCNK5	KCNMA1	Q12791	460
KCNK5	KCNA4	P22459	452
KCNK5	KCNA5	P22460	449
KCNK5	KCNH2	Q12809	433
KCNK5	ABCG8	Q9H221	432
KCNK5	KCNJ10	P78508	428

IntAct

84 interactions, top by confidence:

A	B	Type	Score
LHFPL5	KCNK5	psi-mi:“MI:0915”(physical association)	0.560
CMTM5	KCNK5	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TM4SF4	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	AQP1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	KCNK5	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	KCNK5	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	STRIT1	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TMEM176A	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TMEM128	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	ATP5PF	psi-mi:“MI:0915”(physical association)	0.560
CYB5B	KCNK5	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	VAMP3	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	GJB2	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	SLC66A2	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	BNIP2	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	ORMDL3	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	COMT	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	TSPAN33	psi-mi:“MI:0915”(physical association)	0.560
KCNK5	IGFBP5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (36): KCNK5 (Reconstituted Complex), KCNK5 (Affinity Capture-RNA), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid), KCNK5 (Two-hybrid)

ESM2 similar proteins: A6H8H5, B1WAZ8, O18868, O43525, O43526, O54928, O70344, O75159, O88866, O88943, O88944, O95279, P15385, P15387, P19024, P22462, P51787, P56696, P57058, Q03717, Q14721, Q14B80, Q3UUF8, Q4ZHA6, Q5JV73, Q61762, Q62897, Q63099, Q68UT7, Q76N89, Q8K3F6, Q8K4P8, Q92831, Q92953, Q95167, Q95L11, Q96PR1, Q9JHD1, Q9JK45, Q9JK96

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

858 predictions. Top by Δscore:

Variant	Effect	Δscore
6:39191753:CAC:C	acceptor_gain	1.0000
6:39191755:CCTGA:C	acceptor_loss	1.0000
6:39191756:C:CA	acceptor_loss	1.0000
6:39194164:CTCA:C	donor_loss	1.0000
6:39194166:CA:C	donor_loss	1.0000
6:39194167:A:AC	donor_gain	1.0000
6:39194167:ACCGG:A	donor_gain	1.0000
6:39194168:C:CA	donor_gain	1.0000
6:39194168:CCG:C	donor_gain	1.0000
6:39194168:CCGG:C	donor_gain	1.0000
6:39194168:CCGGC:C	donor_gain	1.0000
6:39194179:G:C	donor_gain	1.0000
6:39194335:CCG:C	acceptor_gain	1.0000
6:39194336:CG:C	acceptor_gain	1.0000
6:39194336:CGC:C	acceptor_gain	1.0000
6:39194338:C:CC	acceptor_gain	1.0000
6:39194602:CACCT:C	donor_gain	1.0000
6:39195871:CTTA:C	donor_loss	1.0000
6:39195872:TTACC:T	donor_loss	1.0000
6:39195874:A:AC	donor_gain	1.0000
6:39195874:AC:A	donor_gain	1.0000
6:39195875:C:CA	donor_gain	1.0000
6:39195875:CC:C	donor_gain	1.0000
6:39195875:CCA:C	donor_gain	1.0000
6:39195875:CCAA:C	donor_gain	1.0000
6:39195875:CCAAT:C	donor_gain	1.0000
6:39195983:ACCAC:A	acceptor_gain	1.0000
6:39195984:CCAC:C	acceptor_gain	1.0000
6:39195984:CCACC:C	acceptor_gain	1.0000
6:39195985:CAC:C	acceptor_gain	1.0000

AlphaMissense

3260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:39191681:A:G	W237R	1.000
6:39191681:A:T	W237R	1.000
6:39195925:C:A	W83C	1.000
6:39195925:C:G	W83C	1.000
6:39195927:A:G	W83R	1.000
6:39195927:A:T	W83R	1.000
6:39191671:A:G	L240P	0.999
6:39191686:A:G	L235P	0.999
6:39191690:C:A	G234W	0.999
6:39191690:C:G	G234R	0.999
6:39191690:C:T	G234R	0.999
6:39191702:A:G	W230R	0.999
6:39191702:A:T	W230R	0.999
6:39194183:C:A	G207V	0.999
6:39194189:C:T	G205D	0.999
6:39194226:C:G	G193R	0.999
6:39194294:C:T	G170D	0.999
6:39194295:C:G	G170R	0.999
6:39194674:A:G	W129R	0.999
6:39194674:A:T	W129R	0.999
6:39194683:A:G	C126R	0.999
6:39194694:C:T	G122E	0.999
6:39194695:C:A	G122W	0.999
6:39194695:C:G	G122R	0.999
6:39194695:C:T	G122R	0.999
6:39194727:C:T	G111D	0.999
6:39194742:G:T	P106H	0.999
6:39194760:C:T	G100E	0.999
6:39195884:G:A	T97I	0.999
6:39195901:A:C	F91L	0.999

dbSNP variants (sampled 300 via entrez): RS1000010562 (6:39221312 G>A), RS1000030532 (6:39194878 C>A,G), RS1000079352 (6:39215941 C>A), RS1000189534 (6:39193952 G>A,T), RS1000281101 (6:39200862 GC>G), RS1000341323 (6:39212796 T>C,G), RS1000346700 (6:39221063 A>G), RS1000359037 (6:39204377 A>G), RS1000446743 (6:39198744 G>A), RS1000632947 (6:39216123 A>C), RS1000833048 (6:39204731 C>T), RS1000910233 (6:39189371 C>T), RS1000959845 (6:39216846 C>T), RS1000996808 (6:39223224 TAAGC>T), RS1001097910 (6:39192013 G>C,T)

Disease associations

OMIM: gene MIM:603493 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST001762_540	Obesity-related traits	7.000000e-06
GCST001960_4	Eating disorders	2.000000e-06
GCST002367_10	Social communication problems	5.000000e-06
GCST003116_41	Coronary artery disease	2.000000e-08
GCST003117_10	Myocardial infarction	3.000000e-08
GCST003720_31	Migraine	7.000000e-13
GCST004787_8	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	1.000000e-07
GCST005194_89	Coronary artery disease	5.000000e-10
GCST005195_135	Coronary artery disease	8.000000e-12
GCST005196_98	Coronary artery disease	3.000000e-12
GCST005196_99	Coronary artery disease	3.000000e-08
GCST007094_98	Diastolic blood pressure	9.000000e-10
GCST007833_5	Urolithiasis	5.000000e-10
GCST008790_25	Urinary albumin-to-creatinine ratio	3.000000e-12
GCST008794_63	Urinary albumin-to-creatinine ratio	1.000000e-12
GCST009598_6	Kidney stones	9.000000e-11
GCST009599_15	Kidney stones	3.000000e-07
GCST009640_28	Urinary albumin-to-creatinine ratio	2.000000e-11
GCST010241_226	Apolipoprotein A1 levels	2.000000e-09
GCST010242_207	HDL cholesterol levels	6.000000e-09
GCST010479_1	Coronary artery disease	4.000000e-10
GCST010866_112	Coronary artery disease	2.000000e-15
GCST011154_6	Fasting plasma glucose	6.000000e-06
GCST011365_48	Myocardial infarction	6.000000e-14
GCST012136_2	Hypertension in type 2 diabetes	2.000000e-06
GCST012618_1	Albuminuria	9.000000e-06
GCST90000025_497	Appendicular lean mass	3.000000e-14

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment
EFO:0006336	diastolic blood pressure
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004285	albuminuria
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523157 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
clofilium	Channel blocker	4.6	pIC50
halothane	Activator	3.7	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Coumestrol	affects cotreatment, increases expression, affects reaction	2
Estradiol	decreases reaction, increases expression	2
Nickel	decreases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Tretinoin	increases expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tobacco tar	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
MRK 003	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Vorinostat	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Cadmium	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4322153	Binding	Inhibition of human TASK2 expressed in CHO cells by Inside-out macro-patches based electrophysiology assay	TASK Channels Pharmacology: New Challenges in Drug Design. — J Med Chem

Clinical trials (associated diseases)

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