KCNK7

Summary

KCNK7 (potassium two pore domain channel subfamily K member 7, HGNC:6282) is a protein-coding gene on chromosome 11q13.1, encoding Potassium channel subfamily K member 7 (Q9Y2U2). Probable potassium channel subunit.

This gene encodes a member 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. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10089 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_033347

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6282
Approved symbol	KCNK7
Name	potassium two pore domain channel subfamily K member 7
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	K2p7.1
Ensembl gene	ENSG00000173338
Ensembl biotype	protein_coding
OMIM	603940
Entrez	10089

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000340313, ENST00000342202, ENST00000394216, ENST00000394217, ENST00000525254, ENST00000530380

RefSeq mRNA: 4 — MANE Select: NM_033347 NM_005714, NM_033347, NM_033348, NM_033455

CCDS: CCDS31608, CCDS41673, CCDS8106

Canonical transcript exons

ENST00000340313 — 3 exons

Exon	Start	End
ENSE00000000136	65595454	65595800
ENSE00001191702	65593476	65593874
ENSE00003668634	65592836	65593210

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 94.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1272 / max 47.4965, expressed in 29 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120649	0.1090	23
120648	0.0182	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	94.57	gold quality
skin of leg	UBERON:0001511	93.83	gold quality
zone of skin	UBERON:0000014	92.08	gold quality
lower esophagus mucosa	UBERON:0035834	90.31	gold quality
upper arm skin	UBERON:0004263	87.75	gold quality
penis	UBERON:0000989	83.58	gold quality
nipple	UBERON:0002030	82.36	gold quality
esophagus mucosa	UBERON:0002469	80.61	gold quality
mammalian vulva	UBERON:0000997	78.15	gold quality
gingival epithelium	UBERON:0001949	76.79	silver quality
upper leg skin	UBERON:0004262	75.86	gold quality
skin of hip	UBERON:0001554	75.84	gold quality
gingiva	UBERON:0001828	74.39	silver quality
esophagus	UBERON:0001043	74.17	gold quality
vagina	UBERON:0000996	70.90	gold quality
cerebellar hemisphere	UBERON:0002245	70.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.93	gold quality
cerebellar cortex	UBERON:0002129	69.89	gold quality
blood	UBERON:0000178	69.79	gold quality
ectocervix	UBERON:0012249	69.62	gold quality
mucosa of stomach	UBERON:0001199	69.49	gold quality
left uterine tube	UBERON:0001303	69.00	gold quality
prefrontal cortex	UBERON:0000451	68.37	gold quality
gastrocnemius	UBERON:0001388	68.13	gold quality
cerebellum	UBERON:0002037	68.04	gold quality
right frontal lobe	UBERON:0002810	67.86	gold quality
tibial nerve	UBERON:0001323	67.27	gold quality
monocyte	CL:0000576	67.26	gold quality
lower esophagus	UBERON:0013473	67.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting KCNK7, 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-6825-5P	99.96	69.81	3431
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-6747-3P	97.73	64.84	1596

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnk12l	ENSDARG00000057037
danio_rerio	si:ch211-261a10.5	ENSDARG00000097085
mus_musculus	Kcnk7	ENSMUSG00000024936
rattus_norvegicus	Kcnk7	ENSRNOG00000020784
drosophila_melanogaster	Ork1	FBGN0017561
drosophila_melanogaster	sand	FBGN0033257
drosophila_melanogaster	Task7	FBGN0037690
drosophila_melanogaster	Task6	FBGN0038165
drosophila_melanogaster	CG10864	FBGN0038621
drosophila_melanogaster	CG34396	FBGN0085425
drosophila_melanogaster	CG42340	FBGN0259242
drosophila_melanogaster	CG42594	FBGN0260971
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), KCNK5 (ENSG00000164626), KCNK9 (ENSG00000169427), KCNK3 (ENSG00000171303), KCNK4 (ENSG00000182450), KCNK12 (ENSG00000184261), KCNK18 (ENSG00000186795)

Protein

Protein identifiers

Potassium channel subfamily K member 7 — Q9Y2U2 (reviewed: Q9Y2U2)

All UniProt accessions (3): Q9Y2U2, H0YCM4, H0YEB9

UniProt curated annotations — full annotation on UniProt →

Function. Probable potassium channel subunit. No channel activity observed in vitro as protein remains in the endoplasmic reticulum. May need to associate with an as yet unknown partner in order to reach the plasma membrane.

Subunit / interactions. Homodimer.

Subcellular location. Membrane.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y2U2-1	A	yes
Q9Y2U2-2	B
Q9Y2U2-3	C

RefSeq proteins (4): NP_005705, NP_203133, NP_203134, NP_258416 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003092	2pore_dom_K_chnl_TASK	Family
IPR003280	2pore_dom_K_chnl	Family
IPR005408	2pore_dom_K_chnl_TWIK	Family
IPR013099	K_chnl_dom	Domain

Pfam: PF07885

UniProt features (15 total): splice variant 4, transmembrane region 4, topological domain 3, intramembrane region 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2U2-F1	82.74	0.43

Functional residue map

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

Glycosylation sites (1): 83

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1299308	Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK)
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: 74 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_TANDEM_PORE_DOMAIN_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, CAGGTCC_MIR492, chr11q13, GOBP_MONOATOMIC_CATION_TRANSPORT, YGACNNYACAR_UNKNOWN, CCAGGTT_MIR490, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOMF_NARROW_PORE_CHANNEL_ACTIVITY, GOMF_VOLTAGE_GATED_MONOATOMIC_CATION_CHANNEL_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_GATED_CHANNEL_ACTIVITY

GO Biological Process (4): potassium ion transport (GO:0006813), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), 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), 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
metal ion transport	1
potassium ion transport	1
monoatomic cation transmembrane transport	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
potassium channel activity	1
leak channel activity	1
binding	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNK7	KRT76	Q01546	952
KCNK7	KCNK18	Q7Z418	700
KCNK7	FAM89B	Q8N5H3	503
KCNK7	TIGD3	Q6B0B8	467
KCNK7	KCNK12	Q9HB15	445
KCNK7	EHBP1L1	Q8N3D4	442
KCNK7	KCNK13	Q9HB14	439
KCNK7	SLC25A45	Q8N413	436
KCNK7	TMEM140	Q9NV12	404
KCNK7	KCNG3	Q8TAE7	398
KCNK7	FRMD8	Q9BZ67	391
KCNK7	KCNN1	Q92952	375
KCNK7	KCNS1	Q96KK3	371
KCNK7	KCNK15	Q9H427	365
KCNK7	KCNG1	Q9UIX4	363

IntAct

1 interactions, top by confidence:

A	B	Type	Score
KCNK7	SLC44A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): KCNK7 (Affinity Capture-RNA), KCNK7 (Two-hybrid), RBMXL1 (Affinity Capture-MS), SLC44A1 (Affinity Capture-MS), KCNK7 (Protein-peptide)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

458 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65593471:CTTA:C	donor_loss	1.0000
11:65593472:TTAC:T	donor_loss	1.0000
11:65593473:TAC:T	donor_loss	1.0000
11:65593474:A:AC	donor_gain	1.0000
11:65593474:AC:A	donor_gain	1.0000
11:65593475:C:CC	donor_gain	1.0000
11:65593475:C:G	donor_loss	1.0000
11:65593475:CC:C	donor_gain	1.0000
11:65593475:CCA:C	donor_gain	1.0000
11:65593475:CCAA:C	donor_gain	1.0000
11:65593475:CCAAG:C	donor_gain	1.0000
11:65593875:C:CA	acceptor_loss	0.9900
11:65593876:T:C	acceptor_loss	0.9900
11:65593206:GTAAC:G	acceptor_gain	0.9800
11:65593871:TAAC:T	acceptor_gain	0.9800
11:65593875:C:CC	acceptor_gain	0.9800
11:65593207:TAAC:T	acceptor_gain	0.9700
11:65593209:ACC:A	acceptor_loss	0.9700
11:65593211:C:CG	acceptor_loss	0.9700
11:65593470:ACTT:A	donor_loss	0.9700
11:65593873:AC:A	acceptor_gain	0.9700
11:65593874:CC:C	acceptor_gain	0.9700
11:65593211:C:CC	acceptor_gain	0.9600
11:65593872:AAC:A	acceptor_gain	0.9600
11:65593208:AAC:A	acceptor_gain	0.9500
11:65595448:TCTTA:T	donor_loss	0.9500
11:65595449:CTTAC:C	donor_loss	0.9500
11:65595450:TTACC:T	donor_loss	0.9500
11:65595451:TACCT:T	donor_loss	0.9500
11:65595452:A:T	donor_loss	0.9500

AlphaMissense

1905 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65593561:G:C	S211R	0.938
11:65593561:G:T	S211R	0.938
11:65593563:T:G	S211R	0.938
11:65593831:G:C	F121L	0.900
11:65593831:G:T	F121L	0.900
11:65593833:A:G	F121L	0.900
11:65593573:G:C	F207L	0.880
11:65593573:G:T	F207L	0.880
11:65593575:A:G	F207L	0.880
11:65593578:A:G	C206R	0.878
11:65595479:G:C	F98L	0.877
11:65595479:G:T	F98L	0.877
11:65595481:A:G	F98L	0.877
11:65595623:G:C	F50L	0.875
11:65595623:G:T	F50L	0.875
11:65595625:A:G	F50L	0.875
11:65593196:C:G	G245R	0.856
11:65593196:C:T	G245R	0.856
11:65593576:G:C	C206W	0.855
11:65593654:G:C	S180R	0.855
11:65593654:G:T	S180R	0.855
11:65593656:T:G	S180R	0.855
11:65595470:G:C	S101R	0.848
11:65595470:G:T	S101R	0.848
11:65595472:T:G	S101R	0.848
11:65593809:C:G	G129R	0.840
11:65593809:C:T	G129R	0.840
11:65593837:C:A	K119N	0.839
11:65593837:C:G	K119N	0.839
11:65595503:C:A	W90C	0.833

dbSNP variants (sampled 300 via entrez): RS1000860898 (11:65596315 T>C), RS1000889063 (11:65596556 G>C,T), RS1002735291 (11:65596910 C>T), RS1003063963 (11:65596167 C>A), RS1003139102 (11:65596336 G>A), RS1003805269 (11:65592507 T>C), RS1004346101 (11:65597499 C>T), RS1004786388 (11:65593859 G>A), RS1005383474 (11:65595103 G>A,C), RS1006032481 (11:65594457 G>A), RS1006943381 (11:65596033 G>A,T), RS1007206764 (11:65594528 C>T), RS1007251416 (11:65594841 GC>G), RS1007281839 (11:65594744 C>G), RS1007386709 (11:65592469 C>A,G)

Disease associations

OMIM: gene MIM:603940 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST005790_22	Rosacea symptom severity	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009180	rosacea severity 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)

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

Ligand	Action	Affinity	Parameter
dapagliflozin	Activation	4.0	pEC50

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
tebuconazole	decreases expression	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YA68	IDG-HEK293T-KCNK7-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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