UniProt functional annotation for P51787



	UniProt functional annotation for P51787

UniProt code: P51787.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:25441029). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP- induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5- bisphosphate (PubMed:25037568). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.

Function: [Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269|PubMed:9305853}.

Subunit: Tetramer (PubMed:18165683, PubMed:19693805, PubMed:25441029). Heterotetramer with KCNE1; targets to the membrane raft (PubMed:25037568, PubMed:19693805, PubMed:20533308). Interacts (via C- terminus) with CALM; forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (PubMed:18165683, PubMed:25441029). Interacts with AKAP9; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1) to the KCNQ1-KCNE1 complex, allowing PKA-mediated phosphorylation and increase of delayed rectifier potassium channel activity (PubMed:11799244, PubMed:25037568). Interacts with KCNE2; forms a heterooligomer complex that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505, PubMed:20533308). Interacts with AP2M1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131). Interacts with NEDD4L; promotes internalization and decreases I(Ks) currents (PubMed:23529131, PubMed:22024150). Interacts with USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization (PubMed:22024150). Heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Interacts with KCNE3; alters membrane raft localization (PubMed:20533308). Interacts with KCNE4; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity (PubMed:19687231, PubMed:20533308). Interacts with KCNE5; impairs KCNQ1 localization in lipid rafts and only conducts current upon strong and continued depolarization (PubMed:20533308, PubMed:12324418). {ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:11799244, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:19693805, ECO:0000269|PubMed:20533308, ECO:0000269|PubMed:22024150, ECO:0000269|PubMed:23529131, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:25441029}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:21228319, ECO:0000269|PubMed:22024150, ECO:0000269|PubMed:25037568}; Multi-pass membrane protein {ECO:0000269|PubMed:18165683}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:23529131}. Early endosome {ECO:0000269|PubMed:23529131}. Membrane raft {ECO:0000269|PubMed:20533308, ECO:0000269|PubMed:24855057}. Endoplasmic reticulum {ECO:0000269|PubMed:21228319, ECO:0000269|PubMed:24855057}. Basolateral cell membrane {ECO:0000269|PubMed:21228319}. Note=Colocalized with KCNE3 at the plasma membrane (PubMed:10646604). Upon 17beta-oestradiol treatment, colocalizes with RAB5A at early endosome (PubMed:23529131). Heterotetramer with KCNQ5 is highly retained at the endoplasmic reticulum and is localized outside of lipid raft microdomains (PubMed:24855057). During the early stages of epithelial cell polarization induced by the calcium switch it removed from plasma membrane to the endoplasmic reticulum where it retained and it is redistributed to the basolateral cell surface in a PI3K-dependent manner at a later stage (PubMed:21228319). {ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:21228319, ECO:0000269|PubMed:23529131, ECO:0000269|PubMed:24855057}.

Tissue specificity: Abundantly expressed in heart, pancreas, prostate, kidney, small intestine and peripheral blood leukocytes. Less abundant in placenta, lung, spleen, colon, thymus, testis and ovaries.

Domain: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Domain: The coiled-coil domain mediates tetramerization. {ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:19693805}.

Domain: The segment S6 is involved in the inhibition of voltage-gated potassium channel activity by KCNE4. {ECO:0000269|PubMed:19687231}.

Domain: The C-terminal assembly domain promotes self-interactiona; allows functional channel. {ECO:0000269|PubMed:10654932}.

Domain: The C-terminal coiled-coil domain interacts with a single CALM molecule via the first two membrane-proximal helical regions, with CALM forming a clamp-like structure. Binding of CALM C-terminus to the first helical region is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to the second helical region is calcium-dependent and regulates electrophysiological activity of the channel. {ECO:0000269|PubMed:25441029}.

Ptm: Phosphorylation at Ser-27 by PKA; increases delayed rectifier potassium channel activity of the KCNQ1-KCNE1 complex through a macromolecular complex that includes PKA, PP1, and the targeting protein AKAP9. {ECO:0000269|PubMed:11799244, ECO:0000269|PubMed:25037568}.

Ptm: Ubiquitinated by NEDD4L; promotes internalization (PubMed:22024150). The ubiquitinylated form is internalized through a clathrin-mediated endocytosis by interacting with AP2M1 and is recycled back to the cell membrane via RAB4A and RAB11A (PubMed:23529131). {ECO:0000269|PubMed:22024150, ECO:0000269|PubMed:23529131}.

Ptm: Deubiquitinated by USP2; counteracts the NEDD4L-specific down- regulation of I(Ks) and restores the membrane localization. {ECO:0000269|PubMed:22024150}.

Disease: Long QT syndrome 1 (LQT1) [MIM:192500]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:10024302, ECO:0000269|PubMed:10220144, ECO:0000269|PubMed:10220146, ECO:0000269|PubMed:10367071, ECO:0000269|PubMed:10409658, ECO:0000269|PubMed:10482963, ECO:0000269|PubMed:10728423, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11799244, ECO:0000269|PubMed:12442276, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18165683, ECO:0000269|PubMed:18400097, ECO:0000269|PubMed:19540844, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:19808498, ECO:0000269|PubMed:21241800, ECO:0000269|PubMed:24184248, ECO:0000269|PubMed:24269949, ECO:0000269|PubMed:24713462, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:25139741, ECO:0000269|PubMed:25705178, ECO:0000269|PubMed:8528244, ECO:0000269|PubMed:8818942, ECO:0000269|PubMed:8872472, ECO:0000269|PubMed:9024139, ECO:0000269|PubMed:9272155, ECO:0000269|PubMed:9302275, ECO:0000269|PubMed:9312006, ECO:0000269|PubMed:9323054, ECO:0000269|PubMed:9386136, ECO:0000269|PubMed:9482580, ECO:0000269|PubMed:9570196, ECO:0000269|PubMed:9641694, ECO:0000269|PubMed:9693036, ECO:0000269|PubMed:9702906, ECO:0000269|PubMed:9799083, ECO:0000269|PubMed:9927399, ECO:0000269|Ref.32}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Jervell and Lange-Nielsen syndrome 1 (JLNS1) [MIM:220400]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. {ECO:0000269|PubMed:10090886, ECO:0000269|PubMed:10728423, ECO:0000269|PubMed:18400097, ECO:0000269|PubMed:18441444, ECO:0000269|PubMed:25705178, ECO:0000269|PubMed:9781056}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Atrial fibrillation, familial, 3 (ATFB3) [MIM:607554]: An autosomal dominant form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:12522251}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Short QT syndrome 2 (SQT2) [MIM:609621]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. {ECO:0000269|PubMed:15159330}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:18711366, ECO:0000269|PubMed:18711367, ECO:0000269|PubMed:24390345}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous: Mutagenesis experiments were carried out by expressing in Xenopus oocytes or COS-7 cells KCNQ1 mutants either individually (homomultimers) or in combination with both wild-type KCNQ1 (mut/wt homomultimers) and minK (heteromultimers).

Similarity: Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAC51781.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAA34739.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:25441029). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP- induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5- bisphosphate (PubMed:25037568). {ECO:0000250\|UniProtKB:P97414, ECO:0000250\|UniProtKB:Q9Z0N7, ECO:0000269\|PubMed:10646604, ECO:0000269\|PubMed:10713961, ECO:0000269\|PubMed:11101505, ECO:0000269\|PubMed:12324418, ECO:0000269\|PubMed:19687231, ECO:0000269\|PubMed:24855057, ECO:0000269\|PubMed:25037568, ECO:0000269\|PubMed:8900283, ECO:0000269\|PubMed:9108097, ECO:0000269\|PubMed:9312006}.



Function:		[Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269\|PubMed:9305853}.


Subunit:		Tetramer (PubMed:18165683, PubMed:19693805, PubMed:25441029). Heterotetramer with KCNE1; targets to the membrane raft (PubMed:25037568, PubMed:19693805, PubMed:20533308). Interacts (via C- terminus) with CALM; forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (PubMed:18165683, PubMed:25441029). Interacts with AKAP9; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1) to the KCNQ1-KCNE1 complex, allowing PKA-mediated phosphorylation and increase of delayed rectifier potassium channel activity (PubMed:11799244, PubMed:25037568). Interacts with KCNE2; forms a heterooligomer complex that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505, PubMed:20533308). Interacts with AP2M1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131). Interacts with NEDD4L; promotes internalization and decreases I(Ks) currents (PubMed:23529131, PubMed:22024150). Interacts with USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization (PubMed:22024150). Heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Interacts with KCNE3; alters membrane raft localization (PubMed:20533308). Interacts with KCNE4; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity (PubMed:19687231, PubMed:20533308). Interacts with KCNE5; impairs KCNQ1 localization in lipid rafts and only conducts current upon strong and continued depolarization (PubMed:20533308, PubMed:12324418). {ECO:0000269\|PubMed:11101505, ECO:0000269\|PubMed:11799244, ECO:0000269\|PubMed:12324418, ECO:0000269\|PubMed:18165683, ECO:0000269\|PubMed:19687231, ECO:0000269\|PubMed:19693805, ECO:0000269\|PubMed:20533308, ECO:0000269\|PubMed:22024150, ECO:0000269\|PubMed:23529131, ECO:0000269\|PubMed:24855057, ECO:0000269\|PubMed:25037568, ECO:0000269\|PubMed:25441029}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:10646604, ECO:0000269\|PubMed:18165683, ECO:0000269\|PubMed:21228319, ECO:0000269\|PubMed:22024150, ECO:0000269\|PubMed:25037568}; Multi-pass membrane protein {ECO:0000269\|PubMed:18165683}. Cytoplasmic vesicle membrane {ECO:0000269\|PubMed:18165683, ECO:0000269\|PubMed:23529131}. Early endosome {ECO:0000269\|PubMed:23529131}. Membrane raft {ECO:0000269\|PubMed:20533308, ECO:0000269\|PubMed:24855057}. Endoplasmic reticulum {ECO:0000269\|PubMed:21228319, ECO:0000269\|PubMed:24855057}. Basolateral cell membrane {ECO:0000269\|PubMed:21228319}. Note=Colocalized with KCNE3 at the plasma membrane (PubMed:10646604). Upon 17beta-oestradiol treatment, colocalizes with RAB5A at early endosome (PubMed:23529131). Heterotetramer with KCNQ5 is highly retained at the endoplasmic reticulum and is localized outside of lipid raft microdomains (PubMed:24855057). During the early stages of epithelial cell polarization induced by the calcium switch it removed from plasma membrane to the endoplasmic reticulum where it retained and it is redistributed to the basolateral cell surface in a PI3K-dependent manner at a later stage (PubMed:21228319). {ECO:0000269\|PubMed:10646604, ECO:0000269\|PubMed:21228319, ECO:0000269\|PubMed:23529131, ECO:0000269\|PubMed:24855057}.
Tissue specificity:		Abundantly expressed in heart, pancreas, prostate, kidney, small intestine and peripheral blood leukocytes. Less abundant in placenta, lung, spleen, colon, thymus, testis and ovaries.
Domain:		The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Domain:		The coiled-coil domain mediates tetramerization. {ECO:0000269\|PubMed:18165683, ECO:0000269\|PubMed:19693805}.
Domain:		The segment S6 is involved in the inhibition of voltage-gated potassium channel activity by KCNE4. {ECO:0000269\|PubMed:19687231}.
Domain:		The C-terminal assembly domain promotes self-interactiona; allows functional channel. {ECO:0000269\|PubMed:10654932}.
Domain:		The C-terminal coiled-coil domain interacts with a single CALM molecule via the first two membrane-proximal helical regions, with CALM forming a clamp-like structure. Binding of CALM C-terminus to the first helical region is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to the second helical region is calcium-dependent and regulates electrophysiological activity of the channel. {ECO:0000269\|PubMed:25441029}.
Ptm:		Phosphorylation at Ser-27 by PKA; increases delayed rectifier potassium channel activity of the KCNQ1-KCNE1 complex through a macromolecular complex that includes PKA, PP1, and the targeting protein AKAP9. {ECO:0000269\|PubMed:11799244, ECO:0000269\|PubMed:25037568}.
Ptm:		Ubiquitinated by NEDD4L; promotes internalization (PubMed:22024150). The ubiquitinylated form is internalized through a clathrin-mediated endocytosis by interacting with AP2M1 and is recycled back to the cell membrane via RAB4A and RAB11A (PubMed:23529131). {ECO:0000269\|PubMed:22024150, ECO:0000269\|PubMed:23529131}.
Ptm:		Deubiquitinated by USP2; counteracts the NEDD4L-specific down- regulation of I(Ks) and restores the membrane localization. {ECO:0000269\|PubMed:22024150}.
Disease:		Long QT syndrome 1 (LQT1) [MIM:192500]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269\|PubMed:10024302, ECO:0000269\|PubMed:10220144, ECO:0000269\|PubMed:10220146, ECO:0000269\|PubMed:10367071, ECO:0000269\|PubMed:10409658, ECO:0000269\|PubMed:10482963, ECO:0000269\|PubMed:10728423, ECO:0000269\|PubMed:10973849, ECO:0000269\|PubMed:11799244, ECO:0000269\|PubMed:12442276, ECO:0000269\|PubMed:15840476, ECO:0000269\|PubMed:16414944, ECO:0000269\|PubMed:16922724, ECO:0000269\|PubMed:18165683, ECO:0000269\|PubMed:18400097, ECO:0000269\|PubMed:19540844, ECO:0000269\|PubMed:19716085, ECO:0000269\|PubMed:19808498, ECO:0000269\|PubMed:21241800, ECO:0000269\|PubMed:24184248, ECO:0000269\|PubMed:24269949, ECO:0000269\|PubMed:24713462, ECO:0000269\|PubMed:25037568, ECO:0000269\|PubMed:25139741, ECO:0000269\|PubMed:25705178, ECO:0000269\|PubMed:8528244, ECO:0000269\|PubMed:8818942, ECO:0000269\|PubMed:8872472, ECO:0000269\|PubMed:9024139, ECO:0000269\|PubMed:9272155, ECO:0000269\|PubMed:9302275, ECO:0000269\|PubMed:9312006, ECO:0000269\|PubMed:9323054, ECO:0000269\|PubMed:9386136, ECO:0000269\|PubMed:9482580, ECO:0000269\|PubMed:9570196, ECO:0000269\|PubMed:9641694, ECO:0000269\|PubMed:9693036, ECO:0000269\|PubMed:9702906, ECO:0000269\|PubMed:9799083, ECO:0000269\|PubMed:9927399, ECO:0000269\|Ref.32}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Jervell and Lange-Nielsen syndrome 1 (JLNS1) [MIM:220400]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. {ECO:0000269\|PubMed:10090886, ECO:0000269\|PubMed:10728423, ECO:0000269\|PubMed:18400097, ECO:0000269\|PubMed:18441444, ECO:0000269\|PubMed:25705178, ECO:0000269\|PubMed:9781056}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Atrial fibrillation, familial, 3 (ATFB3) [MIM:607554]: An autosomal dominant form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269\|PubMed:12522251}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Short QT syndrome 2 (SQT2) [MIM:609621]: A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. {ECO:0000269\|PubMed:15159330}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269\|PubMed:18711366, ECO:0000269\|PubMed:18711367, ECO:0000269\|PubMed:24390345}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Miscellaneous:		Mutagenesis experiments were carried out by expressing in Xenopus oocytes or COS-7 cells KCNQ1 mutants either individually (homomultimers) or in combination with both wild-type KCNQ1 (mut/wt homomultimers) and minK (heteromultimers).
Similarity:		Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAC51781.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAA34739.1; Type=Frameshift; Evidence={ECO:0000305};