IUPHAR DATABASE | Voltage-gated potassium channels

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K_v7.1

Family: Voltage-gated potassium channels

Contents:

Gene and Protein Information

Previous and Unofficial Names

Database Links

Associated Proteins

Ion Selectivity and Conductance

Physiological Functions

Phenotypes, Alleles and Disease Models

Clinically-Relevant Mutations and Pathophysiology

Gene Expression and Pathophysiology

Biologically Significant Variants

References

Gene and Protein Information
Species	TM	P Loops	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	6	1	676	11p15.5	KCNQ1	potassium voltage-gated channel, KQT-like subfamily, member 1	33,37
Mouse	6	1	668	7 F5	Kcnq1	potassium voltage-gated channel, subfamily Q, member 1	3
Rat	6	1	669	1q41	Kcnq1	potassium voltage-gated channel, KQT-like subfamily, member 1	16

Previous and Unofficial Names
slow delayed rectifier
Kv7.1
KCNA8
KCNA9
KVLQT1
LQT
KCNA8
JLNS1
LQT1
Jervell and Lange-Nielsen syndrome 1
IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1
KQT-like 1
potassium voltage-gated channel subfamily KQT member 1
potassium voltage-gated channel, KQT-like subfamily, member 1
potassium voltage-gated channel, subfamily Q, member 1
voltage-gated potassium channel subunit Kv7.1
AW559127

Previous and Unofficial Names

slow delayed rectifier

Kv7.1

KCNA8

KCNA9

KVLQT1

LQT

KCNA8

JLNS1

LQT1

Jervell and Lange-Nielsen syndrome 1

IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1

KQT-like 1

potassium voltage-gated channel subfamily KQT member 1

potassium voltage-gated channel, KQT-like subfamily, member 1

potassium voltage-gated channel, subfamily Q, member 1

voltage-gated potassium channel subunit Kv7.1

AW559127

Database Links
ChEMBL Target	12930 (Hs)
DrugBank Target	741 (Hs)
Ensembl	ENSG00000053918 (Hs), ENSMUSG00000009545 (Mm), ENSRNOG00000020532 (Rn)
Entrez Gene	3784 (Hs), 16535 (Mm), 84020 (Rn)
GeneCards	KCNQ1 (Hs)
GenitoUrinary Development Molecular Anatomy Project	Kcnq1 (Mm)
HomoloGene	85014 (Hs)
Human Protein Reference Database	06341 (Hs)
InterPro	P51787 (Hs), P97414 (Mm), Q9Z0N7 (Rn)
KEGG Gene	hsa:3784 (Hs), mmu:16535 (Mm), rno:84020 (Rn)
OMIM	607542 (Hs)
Orphanet Gene	ORPHA122800 (Hs)
PharmGKB Gene	PA223 (Hs)
PhosphoSitePlus	P51787 (Hs), P97414 (Mm)
Protein Ontology (PRO)	PRO:000000728 (Hs)
RefSeq Nucleotide	NM_000218 (Hs), NM_181798 (Hs), NM_008434 (Mm), NM_032073 (Rn)
RefSeq Protein	NP_000209 (Hs), NP_032460 (Mm), NP_114462 (Rn)
TreeFam	ENSG00000053918 (Hs), ENSMUSG00000009545 (Mm), ENSRNOG00000020532 (Rn)
UniGene Hs.	95162 (Hs)
UniProt	P51787 (Hs), P97414 (Mm), Q9Z0N7 (Rn)
Wikipedia	K_v7.1
	Potassium channels

Search for 3D structures on the PDB
Search by keyword: Voltage-gated potassium channels K_v7.1	Search by accession number: Q9Z0N7, P97414, P51787

Associated Proteins

Heteromeric Pore-forming Subunits
Name	References
Not determined

Auxiliary Subunits
Name	References
KCNE5, minK-related peptide 4 (MiRP4)	2
KCNE4, minK-related peptide 3 (MiRP3)	11
KCNE3, minK-related peptide 2 (MiRP2)	27
KCNE1 (minK/IsK)	3
KCNE2, minK-related peptide 1 (MiRP1)	35

Other Associated Proteins
Name	References
Yotiao	21
Protein kinase A	21
Protein phosphatase 1	21

Associated Protein Comments

Yotiao – targets Protein kinase A and protein phosphatase 1 to KCNQ1 [7,21]

Ion Selectivity and Conductance

Species:	Human
Rank order:	K⁺ > Rb⁺ > Cs⁺ > Na⁺
References:	34

Species:	Human
Single channel conductance (pS):	1.8
References:	23

Ion Selectivity and Conductance Comments

cation selectivity rank order is K+>Rb+>Cs+>Na+ (IKs KCNQ1) [30,34,38] .
heteromeric KvLQT1/minK channels expressed in Xenopus oocytes show a threefold larger conductance (5.8 pS) . [23]

Voltage Dependence

	V_0.5 (mV)	τ (msec)	Reference	Cell type	Species
Activation	9.0	360.0 – 8500.0	19	Ventricular myocytes	Human
Inactivation	-	-		Ventricular myocytes	Human
Comments	Native IKs; tau at +50 mV

	V_0.5 (mV)	τ (msec)	Reference	Cell type	Species
Activation	-23.0	70.0 – 900.0	31	Xenopus laevis oocyte	Human
Inactivation	-18.0	13.0	31	Xenopus laevis oocyte	Human
Comments	KCNQ1 alone; tau @ +20 mV

	V_0.5 (mV)	τ (msec)	Reference	Cell type	Species
Activation	8.0	0.68 – 8.0	26	Xenopus laevis oocyte	Human
Inactivation	-	-		Xenopus laevis oocyte	Human
Comments	KCNQ1+KCNE1; tau @ +40 mV

Associated subunits (Human)
minK and MiRP2

Associated subunits (Human)

minK and MiRP2

Activators

Key to terms and symbols

View all chemical structures

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Ligand	Sp.	Affinity	Units	Concentration range (M)	Holding voltage (mV)	Reference
PIP₂	Hs	-	-	-	-	20
mefenamic acid	Hs	-	-	1x10^-4	-	1
niflumic acid	Hs	-	-	1x10^-4	-	6
R-L3	Hs	6.0	pEC₅₀	1x10^-6	-	25
zinc pyrithione	Hs	5.0	pEC₅₀	1x10^-5	-	36

Pore Blockers

Key to terms and symbols

View all chemical structures

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Ligand	Sp.	Affinity	Units	Concentration range (M)	Holding voltage (mV)	Reference
XE991	Hs	6.11	pK_d	-	-	32
IKs124	Hs	8.1	pIC₅₀	-	-	12
HMR-1556	Hs	7.08	pIC₅₀	-	-	10
L735821	Hs	6.76 – 7.46 (median: 7.0)	pIC₅₀	-	-	28-29
azimilide	Mm	5.25	pIC₅₀	-	-	5
chromanol 293B	Hs	5.04	pIC₅₀	-	-	10

View species-specific pore blocker tables

Pore Blocker Comments

Block is for KCNQ1+KCNE1 channels; block of KCNQ1 alone is ~10-x more potent for XE991, ~10-x less potent for 293B or azimilide

Tissue Distribution

heart = pancreas > kidney > lung = placenta

Species:	Human
Technique:	Northern Blot
References:	33

heart, pancreas, intestine, stomach, kidney, lung, liver, thymus

Species:	Mouse
Technique:	In situ hybridisation
References:	9

Functional Assays

Cardiac action potentials

Species:	Rat
Tissue:	embryonic or neonatal hearts
Response measured:	prolonged action potentials
References:

Physiological Functions

Repolarization of cardiac action potentials

Species:	Human
Tissue:	atrial, ventriclular
References:	3,26

luminal secretion of K+ into endolymphatic space of inner ear

Species:	Mouse
Tissue:	apical surface of vestibular dark cells of inner ear
References:	22,24

When KCNQ1 coassembles with KCNE3, it forms a constitutively open channel that strongly resembles intestinal cAMP-stimulated potassium channel involved in chloride secretion

Species:	Human
Tissue:	intestine (crypt cells)
References:	27

Phenotypes, Alleles and Disease Models

Mouse data from MGI

Click here to show/hide data

Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004308	abnormal basilar membrane	PMID: 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004140	abnormal chief cell morphology	PMID: 11120752
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0000031	abnormal cochlea morphology
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0003308	abnormal cochlear sensory epithelium morphology	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004249	abnormal crista ampullaris morphology	PMID: 15891643
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0004409	abnormal crista ampullaris neuroepithelium morphology	PMID: 11226272
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0001406	abnormal gait
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0003892	abnormal gastric gland	PMID: 11120752
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0005209	abnormal gastric mucosa morphology	PMID: 11120752
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004139	abnormal gastric parietal cell morphology	PMID: 11120752
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0010508	abnormal heart electrocardiography waveform feature	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0010508	abnormal heart electrocardiography waveform feature	PMID: 11226272
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0002729	abnormal inner ear canal morphology	PMID: 11226272
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0000026	abnormal inner ear morphology	PMID: 11226272
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0000035	abnormal membranous labyrinth	PMID: 15498462
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004138	abnormal mucous neck cell morphology	PMID: 11120752
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0002894	abnormal otolith morphology
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0002894	abnormal otolith morphology	PMID: 15891643
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0006089	abnormal saccule morphology	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0002428	abnormal semicircular canal	PMID: 11120752
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0000048	abnormal stria vascularis	PMID: 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0003149	abnormal tectorial membrane morphology	PMID: 15891643
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0010505	abnormal T wave	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0006090	abnormal utricle morphology	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004427	abnormal vestibular labyrinth	PMID: 15891643
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0000034	abnormal vestibule morphology
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0000034	abnormal vestibule morphology	PMID: 11120752
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0004763	absent brainstem auditory evoked potential	PMID: 15498462
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004763	absent brainstem auditory evoked potential	PMID: 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004405	absent cochlear hair cells	PMID: 11120752 15891643
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0004737	absent distortion product otoacoustic emissions	PMID: 15498462
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004301	absent organ of Corti supporting cells	PMID: 11120752 15891643
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0006358	absent pinna reflex	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0006358	absent pinna reflex	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004325	absent vestibular hair cells	PMID: 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004518	absent vestibular hair cell stereocilia	PMID: 15891643
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001395	bi-directional circling	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0001395	bi-directional circling	PMID: 11226272
Kcnq1^vtg-4J	Kcnq1^vtg-4J/Kcnq1^vtg-4J B6.NOD-Kcnq1/J	MGI:108083	MP:0001395	bi-directional circling
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0001625	cardiac hypertrophy	PMID: 11226272
Kcnq1^vtg-2J	Kcnq1^vtg-2J/Kcnq1^vtg-2J C3H/HeJ	MGI:108083	MP:0001394	circling
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0001394	circling
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0001394	circling	PMID: 11120752 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0002857	cochlear ganglion degeneration	PMID: 15891643
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0004398	cochlear inner hair cell degeneration	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0004398	cochlear inner hair cell degeneration	PMID: 11226272
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0004404	cochlear outer hair cell degeneration	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0004404	cochlear outer hair cell degeneration	PMID: 11226272
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0006024	collapsed Reissner membrane	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0006024	collapsed Reissner membrane	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0006024	collapsed Reissner membrane	PMID: 11120752 15891643
Kcnq1^vtg-2J	Kcnq1^vtg-2J/Kcnq1^vtg-2J C3H/HeJ	MGI:108083	MP:0001967	deafness
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001967	deafness	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0001967	deafness	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0001967	deafness	PMID: 15891643
Kcnq1^vtg-4J	Kcnq1^vtg-4J/Kcnq1^vtg-4J B6.NOD-Kcnq1/J	MGI:108083	MP:0001967	deafness
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001262	decreased body weight	PMID: 15498462
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0003145	detached otolithic membrane	PMID: 11120752 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0003883	enlarged stomach	PMID: 11120752
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001410	head bobbing	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0001410	head bobbing	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0001410	head bobbing	PMID: 11120752 15891643
Kcnq1^vtg-2J	Kcnq1^vtg-2J/Kcnq1^vtg-2J C3H/HeJ	MGI:108083	MP:0005307	head tossing
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0005307	head tossing
Kcnq1^vtg-4J	Kcnq1^vtg-4J/Kcnq1^vtg-4J B6.NOD-Kcnq1/J	MGI:108083	MP:0005307	head tossing
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001399	hyperactivity	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0001399	hyperactivity	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0001399	hyperactivity	PMID: 11120752 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0008001	hypochlorhydria	PMID: 11120752
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0001525	impaired balance
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001405	impaired coordination	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0001523	impaired righting response	PMID: 11226272
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0001522	impaired swimming	PMID: 15498462
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004731	increased circulating gastrin level	PMID: 11120752
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0002833	increased heart weight	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0008006	increased stomach pH	PMID: 11120752
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0005211	increased thickness of gastric mucosa	PMID: 11120752
Kcnq1^tm4Kpfe	Kcnq1^tm4Kpfe/Kcnq1^tm4Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0002169	no abnormal phenotype detected	PMID: 15498462
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0000043	organ of Corti degeneration	PMID: 11120752 15891643
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0003896	prolonged PR interval	PMID: 11226272
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0010392	prolonged QRS complex duration	PMID: 11226272
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0003233	prolonged QT interval	PMID: 15498462
Kcnq1^tm3Kpfe	Kcnq1^tm3Kpfe/Kcnq1^tm3Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0003233	prolonged QT interval	PMID: 15498462
Kcnq1⁺\|Kcnq1^tm3Kpfe	Kcnq1^tm3Kpfe/Kcnq1⁺ involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0003233	prolonged QT interval	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0003233	prolonged QT interval	PMID: 11226272
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0010323	retropulsion
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0008308	small scala media	PMID: 11120752 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0001411	spinning	PMID: 15891643
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0001408	stereotypic behavior	PMID: 11120752
Kcnq1^tm2Kpfe	Kcnq1^tm2Kpfe/Kcnq1^tm2Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:108083	MP:0006330	syndromic hearing impairment	PMID: 15498462
Kcnq1^tm1Kpfe	Kcnq1^tm1Kpfe/Kcnq1^tm1Kpfe involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:108083	MP:0006330	syndromic hearing impairment	PMID: 11226272
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004364	thin stria vascularis	PMID: 15891643
Kcnq1^vtg-3J	Kcnq1^vtg-3J/Kcnq1^vtg-3J C57BL/6J-Kcnq1/J	MGI:108083	MP:0000745	tremors
Kcnq1^tm1Apf	Kcnq1^tm1Apf/Kcnq1^tm1Apf involves: 129P2/OlaHsd * C57BL/6	MGI:108083	MP:0004334	utricular macular degeneration	PMID: 15891643

Clinically-Relevant Mutations and Pathophysiology

Disease:	Long QT syndrome (autosomal recessive Romano-Ward syndrome or autosomal recessive Jervell and Lange-Nielsen syndrome)
OMIM:	192500
Orphanet:	101016
Role:	Loss of function mutations in KCNQ1 (or associated KCNE1 beta-subunits) prolongs action potentials and increases risk of torsades de pointes arrhythmia, fibrillation and sudden death; recessive mutations also cause deafness
Drugs:	Activators of KCNQ1 may alleviate condition, but blockers can aggravate LQTS
Therapeutic use:	Activators are being explored as potential therapy for LQTS
References:	15

Click column headers to sort

Type	Species	Molecular location	Description	Reference
Deletion	Human	several
Missense	Human	several		33

Disease:	Short QT syndrome and/or atrial fibrillation
OMIM:	609621
Orphanet:	51083
Role:	Gain of function mutations in KCNQ1 shortens action potentials, leading to shortened QT interval and cardiac arrhythmia
References:	4,13

Click column headers to sort

Type	Species	Molecular location	Description	Reference
Missense	Human	S140G		8
Missense	Human	V307L, V141M		4,13

Disease:	Jervell and Lange-Nielsen syndrome 1; JLNS1
OMIM:	220400
Orphanet:	90647
References:

Mutations not determined

Disease:	Atrial fibrillation, familial, 3; ATFB3
OMIM:	607554
Orphanet:	334
References:

Mutations not determined

Gene Expression and Pathophysiology

Imprinting: early developmental expression is maternal in origin. Maternal repression of Kcnq1 in mouse is controlled by DNA methylation originating in the oocyte

Tissue or cell type:	multiple
Pathophysiology:	deletion of multiple genes in Beckwith-Wiedemann syndrome (overgrowth disorder with increased risk of pediatric tumours); pathology probably unrelated to deletion of KCNQ1
Species:	Mouse
Technique:
References:	17-18

Biologically Significant Variants

Isoform 1

Nucleotide accession:	NM_000218
Protein accession:	NP_000209
Amino acids:	676
Type:	Splice variant
Species:	Human
References:

Isoform 2

Nucleotide accession:	NM_181798
Protein accession:	NP_861463
Amino acids:	549
Type:	Splice variant
Species:	Human
References:	14

Biologically Significant Variant Comments

Variant 1 encodes the predominant isoform 1. Variant 2 differs in the 5' UTR and CDS,compared to variant 1. Isoform 2 has a shorter and distinct N-terminus compared to isoform 1 and causes dominant-negative suppression of KCNQ1 channel function.

REFERENCES

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1. Abbott, GW; Butler, MH; Bendahhou, S; Dalakas, MC; Ptacek, LJ; Goldstein, SA. (2001) MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell, 104 (2): 217-31. [PMID:11207363]

2. Angelo, K; Jespersen, T; Grunnet, M; Nielsen, MS; Klaerke, DA; Olesen, SP. (2002) KCNE5 induces time- and voltage-dependent modulation of the KCNQ1 current. Biophys. J., 83 (4): 1997-2006. [PMID:12324418]

3. Barhanin, J; Lesage, F; Guillemare, E; Fink, M; Lazdunski, M; Romey, G. (1996) K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature, 384 (6604): 78-80. [PMID:8900282]

4. Bellocq, C; van Ginneken, AC; Bezzina, CR; Alders, M; Escande, D; Mannens, MM; Baró, I; Wilde, AA. (2004) Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation, 109 (20): 2394-7. [PMID:15159330]

5. Busch, AE; Busch, GL; Ford, E; Suessbrich, H; Lang, HJ; Greger, R; Kunzelmann, K; Attali, B; Stühmer, W. (1997) The role of the IsK protein in the specific pharmacological properties of the IKs channel complex. Br. J. Pharmacol., 122 (2): 187-9. [PMID:9313924]

6. Busch, AE; Herzer, T; Wagner, CA; Schmidt, F; Raber, G; Waldegger, S; Lang, F. (1994) Positive regulation by chloride channel blockers of IsK channels expressed in Xenopus oocytes. Mol. Pharmacol., 46 (4): 750-3. [PMID:7969055]

7. Chen, L; Kurokawa, J; Kass, RS. (2005) Phosphorylation of the A-kinase-anchoring protein Yotiao contributes to protein kinase A regulation of a heart potassium channel. J. Biol. Chem., 280 (36): 31347-52. [PMID:16002409]

8. Chen, YH; Xu, SJ; Bendahhou, S; Wang, XL; Wang, Y; Xu, WY; Jin, HW; Sun, H; Su, XY; Zhuang, QN; Yang, YQ; Li, YB; Liu, Y; Xu, HJ; Li, XF; Ma, N; Mou, CP; Chen, Z; Barhanin, J; Huang, W. (2003) KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science, 299 (5604): 251-4. [PMID:12522251]

9. Demolombe, S; Franco, D; de Boer, P; Kuperschmidt, S; Roden, D; Pereon, Y; Jarry, A; Moorman, AF; Escande, D. (2001) Differential expression of KvLQT1 and its regulator IsK in mouse epithelia. Am. J. Physiol., Cell Physiol., 280 (2): C359-72. [PMID:11208532]

10. Dong, MQ; Lau, CP; Gao, Z; Tseng, GN; Li, GR. (2006) Characterization of recombinant human cardiac KCNQ1/KCNE1 channels (I (Ks)) stably expressed in HEK 293 cells. J. Membr. Biol., 210 (3): 183-92. [PMID:16909339]

11. Grunnet, M; Jespersen, T; Rasmussen, HB; Ljungstrøm, T; Jorgensen, NK; Olesen, SP; Klaerke, DA. (2002) KCNE4 is an inhibitory subunit to the KCNQ1 channel. J. Physiol. (Lond.), 542 (Pt 1): 119-30. [PMID:12096056]

12. Heitzmann, D; Grahammer, F; von Hahn, T; Schmitt-Gräff, A; Romeo, E; Nitschke, R; Gerlach, U; Lang, HJ; Verrey, F; Barhanin, J; Warth, R. (2004) Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric parietal cells. J. Physiol. (Lond.), 561 (Pt 2): 547-57. [PMID:15579540]

13. Hong, K; Piper, DR; Diaz-Valdecantos, A; Brugada, J; Oliva, A; Burashnikov, E; Santos-de-Soto, J; Grueso-Montero, J; Diaz-Enfante, E; Brugada, P; Sachse, F; Sanguinetti, MC; Brugada, R. (2005) De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc. Res., 68 (3): 433-40. [PMID:16109388]

14. Jiang, M; Tseng-Crank, J; Tseng, GN. (1997) Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart. J. Biol. Chem., 272 (39): 24109-12. [PMID:9305853]

15. Keating, MT; Sanguinetti, MC. (2001) Molecular and cellular mechanisms of cardiac arrhythmias. Cell, 104 (4): 569-80. [PMID:11239413]

16. Kunzelmann, K; Hübner, M; Schreiber, R; Levy-Holzman, R; Garty, H; Bleich, M; Warth, R; Slavik, M; von Hahn, T; Greger, R. (2001) Cloning and function of the rat colonic epithelial K+ channel KVLQT1. J. Membr. Biol., 179 (2): 155-64. [PMID:11220365]

17. Lee, MP; Hu, RJ; Johnson, LA; Feinberg, AP. (1997) Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements. Nat. Genet., 15 (2): 181-5. [PMID:9020845]

18. Lewis, A; Green, K; Dawson, C; Redrup, L; Huynh, KD; Lee, JT; Hemberger, M; Reik, W. (2006) Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo. Development, 133 (21): 4203-10. [PMID:17021040]

19. Li, GR; Feng, J; Yue, L; Carrier, M; Nattel, S. (1996) Evidence for two components of delayed rectifier K+ current in human ventricular myocytes. Circ. Res., 78 (4): 689-96. [PMID:8635226]

20. Loussouarn, G; Park, KH; Bellocq, C; Baró, I; Charpentier, F; Escande, D. (2003) Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels. EMBO J., 22 (20): 5412-21. [PMID:14532114]

21. Marx, SO; Kurokawa, J; Reiken, S; Motoike, H; D'Armiento, J; Marks, AR; Kass, RS. (2002) Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel. Science, 295 (5554): 496-9. [PMID:11799244]

22. Neyroud, N; Tesson, F; Denjoy, I; Leibovici, M; Donger, C; Barhanin, J; Fauré, S; Gary, F; Coumel, P; Petit, C; Schwartz, K; Guicheney, P. (1997) A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat. Genet., 15 (2): 186-9. [PMID:9020846]

23. Pusch, M. (1998) Increase of the single-channel conductance of KvLQT1 potassium channels induced by the association with minK. Pflugers Arch., 437 (1): 172-4. [PMID:9817805]

24. Rivas, A; Francis, HW. (2005) Inner ear abnormalities in a Kcnq1 (Kvlqt1) knockout mouse: a model of Jervell and Lange-Nielsen syndrome. Otol. Neurotol., 26 (3): 415-24. [PMID:15891643]

25. Salata, JJ; Jurkiewicz, NK; Wang, J; Evans, BE; Orme, HT; Sanguinetti, MC. (1998) A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents. Mol. Pharmacol., 54 (1): 220-30. [PMID:9658209]

26. Sanguinetti, MC; Curran, ME; Zou, A; Shen, J; Spector, PS; Atkinson, DL; Keating, MT. (1996) Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature, 384 (6604): 80-3. [PMID:8900283]

27. Schroeder, BC; Waldegger, S; Fehr, S; Bleich, M; Warth, R; Greger, R; Jentsch, TJ. (2000) A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature, 403 (6766): 196-9. [PMID:10646604]

28. Seebohm, G; Chen, J; Strutz, N; Culberson, C; Lerche, C; Sanguinetti, MC. (2003) Molecular determinants of KCNQ1 channel block by a benzodiazepine. Mol. Pharmacol., 64 (1): 70-7. [PMID:12815162]

29. Selnick, HG; Liverton, NJ; Baldwin, JJ; Butcher, JW; Claremon, DA; Elliott, JM; Freidinger, RM; King, SA; Libby, BE; McIntyre, CJ; Pribush, DA; Remy, DC; Smith, GR; Tebben, AJ; Jurkiewicz, NK; Lynch, JJ; Salata, JJ; Sanguinetti, MC; Siegl, PK; Slaughter, DE; Vyas, K. (1997) Class III antiarrhythmic activity in vivo by selective blockade of the slowly activating cardiac delayed rectifier potassium current IKs by (R)-2-(2,4-trifluoromethyl)-N-[2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)- 2, 3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide. J. Med. Chem., 40 (24): 3865-8. [PMID:9397166]

30. Sesti, F; Goldstein, SA. (1998) Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome. J. Gen. Physiol., 112 (6): 651-63. [PMID:9834138]

31. Tristani-Firouzi, M; Sanguinetti, MC. (1998) Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits. J. Physiol. (Lond.), 510 ( Pt 1): 37-45. [PMID:9625865]

32. Wang, HS; Brown, BS; McKinnon, D; Cohen, IS. (2000) Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. Mol. Pharmacol., 57 (6): 1218-23. [PMID:10825393]

33. Wang, Q; Curran, ME; Splawski, I; Burn, TC; Millholland, JM; VanRaay, TJ; Shen, J; Timothy, KW; Vincent, GM; de Jager, T; Schwartz, PJ; Toubin, JA; Moss, AJ; Atkinson, DL; Landes, GM; Connors, TD; Keating, MT. (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat. Genet., 12 (1): 17-23. [PMID:8528244]

34. Wollnik, B; Schroeder, BC; Kubisch, C; Esperer, HD; Wieacker, P; Jentsch, TJ. (1997) Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias. Hum. Mol. Genet., 6 (11): 1943-9. [PMID:9302275]

35. Wu, DM; Jiang, M; Zhang, M; Liu, XS; Korolkova, YV; Tseng, GN. (2006) KCNE2 is colocalized with KCNQ1 and KCNE1 in cardiac myocytes and may function as a negative modulator of I(Ks) current amplitude in the heart. , 3 (12): 1469-80. [PMID:17161791]

36. Xiong, Q; Sun, H; Li, M. (2007) Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat. Chem. Biol., 3 (5): 287-96. [PMID:17435769]

37. Yang, WP; Levesque, PC; Little, WA; Conder, ML; Ramakrishnan, P; Neubauer, MG; Blanar, MA. (1998) Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. J. Biol. Chem., 273 (31): 19419-23. [PMID:9677360]

38. Yang, Y; Sigworth, FJ. (1998) Single-channel properties of IKs potassium channels. J. Gen. Physiol., 112 (6): 665-78. [PMID:9834139]

To cite this database page, please use the following:

K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Michael C. Sanguinetti, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: K_v7.1. Last modified on 28/02/2012. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=560.

Voltage-gated potassium channels
	Introduction
	Contributors
	References
	K_v1.1
	K_v1.2
	K_v1.3
	K_v1.4
	K_v1.5
	K_v1.6
	K_v1.7
	K_v1.8
	K_v2.1
	K_v2.2
	K_v3.1
	K_v3.2
	K_v3.3
	K_v3.4
	K_v4.1
	K_v4.2
	K_v4.3
	K_v5.1
	K_v6.1
	K_v6.2
	K_v6.3
	K_v6.4
	K_v7.1
	K_v7.2
	K_v7.3
	K_v7.4
	K_v7.5
	K_v8.1
	K_v8.2
	K_v9.1
	K_v9.2
	K_v9.3
	K_v10.1
	K_v10.2
	K_v11.1
	K_v11.2
	K_v11.3
	K_v12.1
	K_v12.2
	K_v12.3