KCNQ1

potassium voltage-gated channel subfamily Q member 1, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 11:2444683-2849105

Previous symbols: [ "LQT", "KCNA9" ]

Links

ENSG00000053918 ∙ NCBI:3784 ∙ OMIM:607542 ∙ HGNC:6294 ∙ Uniprot:P51787 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Jervell and Lange-Nielsen syndrome 1 (Strong), mode of inheritance: AR
• Jervell and Lange-Nielsen syndrome 1 (Definitive), mode of inheritance: AR
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• short QT syndrome (Supportive), mode of inheritance: AD
• Jervell and Lange-Nielsen syndrome (Supportive), mode of inheritance: AR
• short QT syndrome type 2 (Strong), mode of inheritance: AD
• long QT syndrome 1 (Definitive), mode of inheritance: AD
• long QT syndrome 1 (Definitive), mode of inheritance: AR
• Jervell and Lange-Nielsen syndrome 1 (Definitive), mode of inheritance: AR
• long QT syndrome 1 (Strong), mode of inheritance: AD
• atrial fibrillation, familial, 3 (Strong), mode of inheritance: AD
• short QT syndrome type 2 (Strong), mode of inheritance: AD
• Jervell and Lange-Nielsen syndrome 1 (Strong), mode of inheritance: AR
• Jervell and Lange-Nielsen syndrome (Definitive), mode of inheritance: AR
• short QT syndrome (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
• long QT syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome 2; Atrial fibrillation, familial 3	AD/AR/Digenic	Audiologic/Otolaryngologic; Cardiovascular	Medical/surgicalmanagement (eg, ICD placement, antiarhythymognic medications) may help prevent/decrease severe sequelae, though cardiac transplantion has been necessary for some individuals; For individuals with JLNS1, recognition and prompt treatment of hearing loss may be beneficial	Audiologic/Otolaryngologic; Cardiovascular	13435203; 4393533; 112730; 7365362; 6991948; 7471361; 1884444; 8892796; 8872472; 8528244; 9020846; 9164812; 9702906; 9593563; 9753711; 10086971; 10077519; 10220144; 10973849; 11140949; 11289718; 11479253; 11433047; 12522251; 12736279; 15159330; 15051636; 16132053; 15890322; 15840476; 16461811; 16922724; 18580685; 19261104; 20301308; 20301579; 21185499; 21952006; 22293141; 22456477; 22708720; 22727609; 22882672; 22885918; 23000022
The age of onset of clinical manifestations may be highly variable; The condition can manifest with hearing loss in JLNS1 in addition to cardiac manifestations; Digenic inheritance (eg, with KCNH2) has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNQ1 gene.

• Long QT syndrome (1145 variants)
• not provided (1002 variants)
• Cardiac arrhythmia (490 variants)
• Cardiovascular phenotype (477 variants)
• Congenital long QT syndrome (362 variants)
• Long QT syndrome 1 (313 variants)
• not specified (183 variants)
• Jervell and Lange-Nielsen syndrome 1 (122 variants)
• Atrial fibrillation, familial, 3 (104 variants)
• Short QT syndrome type 2 (103 variants)
• Jervell and Lange-Nielsen syndrome (31 variants)
• Familial atrial fibrillation (28 variants)
• Short QT syndrome (27 variants)
• Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Beckwith-Wiedemann syndrome;Short QT syndrome type 2;Atrial fibrillation, familial, 3 (21 variants)
• Short QT syndrome type 2;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1 (12 variants)
• KCNQ1-Related Disorders (11 variants)
• Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Short QT syndrome type 2;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1 (7 variants)
• Inborn genetic diseases (7 variants)
• KCNQ1-related condition (6 variants)
• Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1 (5 variants)
• SUDDEN INFANT DEATH SYNDROME (5 variants)
• Jervell and Lange-Nielsen syndrome 1;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Long QT syndrome 1;Short QT syndrome type 2 (5 variants)
• Long QT syndrome 1;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Short QT syndrome type 2;Jervell and Lange-Nielsen syndrome 1 (5 variants)
• Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome (4 variants)
• Atrial fibrillation, familial, 3;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Beckwith-Wiedemann syndrome;Short QT syndrome type 2 (4 variants)
• Prolonged QT interval (3 variants)
• Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2;Atrial fibrillation, familial, 3 (3 variants)
• Wolff-Parkinson-White pattern (3 variants)
• Atrial fibrillation (3 variants)
• Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1 (2 variants)
• Long QT syndrome 1;Short QT syndrome type 2;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1 (2 variants)
• Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2;Long QT syndrome 1 (2 variants)
• Long QT syndrome 1, recessive (2 variants)
• Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1;Short QT syndrome type 2;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome (2 variants)
• Short QT syndrome type 2;Atrial fibrillation, familial, 3;Long QT syndrome 1 (2 variants)
• Congenital long QT syndrome;Jervell and Lange-Nielsen syndrome (2 variants)
• Beckwith-Wiedemann syndrome;Atrial fibrillation, familial, 3;Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1;Short QT syndrome type 2 (2 variants)
• Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Short QT syndrome type 2 (2 variants)
• Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2 (2 variants)
• Long QT syndrome 1;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2 (2 variants)
• Long QT syndrome 1;Short QT syndrome type 2;Atrial fibrillation, familial, 3 (2 variants)
• Atrial fibrillation, familial, 3;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2;Long QT syndrome 1;Beckwith-Wiedemann syndrome (2 variants)
• Conduction disorder of the heart (2 variants)
• Cardiomyopathy (1 variants)
• Short QT syndrome type 2;Long QT syndrome 1;Atrial fibrillation, familial, 3;Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Recurrent spontaneous abortion (1 variants)
• Atrial fibrillation, familial, 3;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2;Long QT syndrome 1 (1 variants)
• Short QT syndrome type 2;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1 (1 variants)
• Ventricular fibrillation (1 variants)
• Atrial fibrillation, familial, 3;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2 (1 variants)
• Beckwith-Wiedemann syndrome;Atrial fibrillation, familial, 3;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Short QT syndrome type 2 (1 variants)
• KCNQ1OT1-related condition (1 variants)
• Long QT syndrome 1;Beckwith-Wiedemann syndrome;Atrial fibrillation, familial, 3;Short QT syndrome type 2;Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Short QT syndrome type 2;Atrial fibrillation, familial, 3;Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1 (1 variants)
• Brugada syndrome (1 variants)
• Autosomal dominant KCNQ1-related disease (1 variants)
• Polymorphic ventricular tachycardia (1 variants)
• Long QT syndrome 1;Atrial fibrillation, familial, 3;Short QT syndrome type 2;Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Long QT syndrome 1;Short QT syndrome type 2;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Atrial fibrillation, familial, 3 (1 variants)
• Short QT syndrome type 2;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome (1 variants)
• Beckwith-Wiedemann syndrome;Short QT syndrome type 2;Atrial fibrillation, familial, 3;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Hypertrophic cardiomyopathy (1 variants)
• Atrial fibrillation, familial, 3;Short QT syndrome type 2;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Beckwith-Wiedemann syndrome (1 variants)
• Long QT syndrome 2 (1 variants)
• Abnormality of the cardiovascular system (1 variants)
• Torsades de pointes (1 variants)
• Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1;Short QT syndrome type 2 (1 variants)
• Ear malformation (1 variants)
• Congenital long QT syndrome;Rare genetic deafness;Jervell and Lange-Nielsen syndrome (1 variants)
• Long QT syndrome 1/2, digenic (1 variants)
• KCNQ1-related epilepsy (1 variants)
• 13 conditions (1 variants)
• Jervell and Lange-Nielsen syndrome;Congenital long QT syndrome (1 variants)
• Sudden cardiac death (1 variants)
• Hearing impairment (1 variants)
• Short QT syndrome type 2;Jervell and Lange-Nielsen syndrome 1;Atrial fibrillation, familial, 3;Beckwith-Wiedemann syndrome;Long QT syndrome 1 (1 variants)
• Long QT syndrome 1;Short QT syndrome type 2;Atrial fibrillation, familial, 3;Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Short QT syndrome type 2;Jervell and Lange-Nielsen syndrome 1;Beckwith-Wiedemann syndrome;Atrial fibrillation, familial, 3;Long QT syndrome 1 (1 variants)
• Atrial fibrillation, familial, 3;Short QT syndrome type 2;Beckwith-Wiedemann syndrome;Jervell and Lange-Nielsen syndrome 1;Long QT syndrome 1 (1 variants)
• Acquired susceptibility to long QT syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNQ1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	292	4	303
missense	61	148	425	9	1	644
nonsense	39	11	2			52
start loss	2					2
frameshift	79	31	4			114
inframe indel	5	2	20	2		29
splice donor/acceptor (+/-2bp)	21	32	1	1		55
splice region	3	5	36	46		90
non coding		2	65	261	297	625
Total	207	226	524	565	302

Highest pathogenic variant AF is 0.0000526

Variants in KCNQ1

This is a list of pathogenic ClinVar variants found in the KCNQ1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-2444714-C-G			Likely benign (Aug 15, 2019)
11-2444984-GC-G			Benign (Mar 03, 2015)
11-2444986-C-A			Benign (Mar 03, 2015)
11-2445030-G-A		Jervell and Lange-Nielsen syndrome 1 • Short QT syndrome type 2 • Congenital long QT syndrome • Atrial fibrillation, familial, 3 • Long QT syndrome 1 • Short QT syndrome type 2;Jervell and Lange-Nielsen syndrome 1;Beckwith-Wiedemann syndrome;Atrial fibrillation, familial, 3;Long QT syndrome 1	Uncertain significance (Aug 27, 2021)
11-2445044-G-C		Atrial fibrillation, familial, 3 • Jervell and Lange-Nielsen syndrome 1 • Long QT syndrome 1 • Short QT syndrome type 2	Uncertain significance (May 01, 2019)
11-2445061-C-T		Short QT syndrome type 2 • Jervell and Lange-Nielsen syndrome 1 • Long QT syndrome 1 • Atrial fibrillation, familial, 3 • Congenital long QT syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-2445073-CG-C		not specified	Likely benign (Apr 07, 2017)
11-2445094-T-C		not specified • Cardiovascular phenotype • Short QT syndrome type 2 • Atrial fibrillation, familial, 3 • Jervell and Lange-Nielsen syndrome 1 • Congenital long QT syndrome • Long QT syndrome 1	Conflicting classifications of pathogenicity (Dec 01, 2023)
11-2445095-C-A		Cardiovascular phenotype	Uncertain significance (Oct 14, 2022)
11-2445096-G-A		Cardiovascular phenotype	Uncertain significance (Apr 06, 2022)
11-2445096-G-C		Cardiovascular phenotype	Uncertain significance (Oct 31, 2022)
11-2445099-A-G		Congenital long QT syndrome	not provided (-)
11-2445099-A-T		Long QT syndrome	Pathogenic (Oct 19, 2022)
11-2445100-T-A			Pathogenic (Feb 03, 2016)
11-2445100-T-C		Congenital long QT syndrome	not provided (-)
11-2445102-G-A			Uncertain significance (-)
11-2445103-C-G		Long QT syndrome 1	Likely pathogenic (Jul 27, 2017)
11-2445103-C-T		Congenital long QT syndrome	Uncertain significance (May 27, 2014)
11-2445105-G-C		Long QT syndrome	Uncertain significance (May 19, 2022)
11-2445106-C-G			Uncertain significance (Dec 31, 2019)
11-2445107-G-A			Likely benign (Feb 01, 2023)
11-2445113-C-T		Long QT syndrome	Likely benign (Oct 06, 2023)
11-2445114-TC-T			Likely pathogenic (Apr 30, 2018)
11-2445117-C-T		Congenital long QT syndrome • Long QT syndrome 1 • not specified • Long QT syndrome • Atrial fibrillation, familial, 3;Long QT syndrome 1;Jervell and Lange-Nielsen syndrome 1;Beckwith-Wiedemann syndrome;Short QT syndrome type 2 • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 01, 2024)
11-2445119-G-A		Long QT syndrome	Likely benign (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNQ1	protein_coding	protein_coding	ENST00000155840	16	404426

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.55e-8	0.990	125664	0	84	125748	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	295	398	0.742	0.0000272	4283
Missense in Polyphen		97	175.73	0.55199		1739
Synonymous	-1.73	206	177	1.17	0.0000131	1420
Loss of Function	2.37	17	31.3	0.543	0.00000152	351

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000645	0.000644
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000164	0.000163
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000406	0.000404
Middle Eastern	0.000164	0.000163
South Asian	0.000331	0.000327
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity) (PubMed:10646604). Associates with KCNE beta subunits that modulates current kinetics (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). 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}.
• Disease: 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.31}. Note=The disease is caused by mutations 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 mutations 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 mutations 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 mutations 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 variations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Antiarrhythmic Pathway, Pharmacodynamics;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;TarBasePathway;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Neuronal System;Phase 2 - plateau phase;Phase 3 - rapid repolarisation;Cardiac conduction;Muscle contraction;TNFalpha;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.337

Intolerance Scores

• loftool: 0.00344
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.32

Haploinsufficiency Scores

• pHI: 0.322
• hipred: Y
• hipred_score: 0.676
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.683

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnq1
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: kcnq1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: regulation of gene expression by genetic imprinting;sensory perception of sound;regulation of heart contraction;positive regulation of heart rate;gene silencing;cellular response to drug;inner ear development;intestinal absorption;cardiac muscle contraction;regulation of membrane repolarization;regulation of ventricular cardiac muscle cell membrane repolarization;regulation of atrial cardiac muscle cell membrane repolarization;positive regulation of cardiac muscle contraction;regulation of gastric acid secretion;renal absorption;cellular response to cAMP;potassium ion transmembrane transport;cellular response to epinephrine stimulus;cardiovascular system development;ventricular cardiac muscle cell action potential;membrane repolarization during action potential;membrane repolarization during cardiac muscle cell action potential;atrial cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;potassium ion export across plasma membrane;membrane repolarization during atrial cardiac muscle cell action potential;membrane repolarization during ventricular cardiac muscle cell action potential;positive regulation of potassium ion transmembrane transport
• Cellular component: cytoplasm;lysosome;early endosome;late endosome;endoplasmic reticulum;plasma membrane;voltage-gated potassium channel complex;integral component of membrane;basolateral plasma membrane;cytoplasmic vesicle membrane;ion channel complex;membrane raft
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;calmodulin binding;phosphatidylinositol-4,5-bisphosphate binding;protein phosphatase 1 binding;outward rectifier potassium channel activity;protein kinase A catalytic subunit binding;protein kinase A regulatory subunit binding;ion channel binding;voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization;scaffold protein binding;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization