KCNE1

potassium voltage-gated channel subfamily E regulatory subunit 1, the group of Potassium voltage-gated channel regulatory subunits

Basic information

Region (hg38): 21:34446687-34512214

Links

ENSG00000180509 ∙ NCBI:3753 ∙ OMIM:176261 ∙ HGNC:6240 ∙ Uniprot:P15382 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Jervell and Lange-Nielsen syndrome 2 (Strong), mode of inheritance: AR
• long QT syndrome 5 (Definitive), mode of inheritance: AD
• Jervell and Lange-Nielsen syndrome (Supportive), mode of inheritance: AR
• Jervell and Lange-Nielsen syndrome 2 (Strong), mode of inheritance: AR
• Jervell and Lange-Nielsen syndrome 2 (Strong), mode of inheritance: AR
• long QT syndrome 5 (Limited), mode of inheritance: AD
• long QT syndrome 5 (Strong), mode of inheritance: AD
• long QT syndrome 5 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Long QT syndrome 5; Jervell and Lange-Nielsen syndrome 2	AD/AR/Digenic	Audiologic/Otolaryngologic; Cardiovascular	Preventive measures and medical management may be helpful to help decrease morbidity related to long-QT syndrome; In JLNS, treatment of deafness may also be beneficial for language and related development	Audiologic/Otolaryngologic; Cardiovascular	13435203; 6991948; 9354802; 9328483; 10973849; 15051636; 14760488; 15840476; 16922724; 20301308; 20301579; 20809527; 21070882
Heterozygous variants cause long QT-syndrome 1 (Ward Romano syndrome); Biallelic variants cause Jervell and Lang-Nielsen syndrome, which includes congenital deafness; Digenic/complex inheritance has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNE1 gene.

• Long QT syndrome (141 variants)
• not provided (123 variants)
• Long QT syndrome 5 (101 variants)
• Jervell and Lange-Nielsen syndrome 2 (98 variants)
• Congenital long QT syndrome (95 variants)
• Cardiovascular phenotype (73 variants)
• not specified (44 variants)
• Jervell and Lange-Nielsen syndrome 2;Long QT syndrome 5 (23 variants)
• Long QT syndrome 5;Jervell and Lange-Nielsen syndrome 2 (18 variants)
• Jervell and Lange-Nielsen syndrome (7 variants)
• Cardiomyopathy (3 variants)
• Inborn genetic diseases (3 variants)
• KCNE1-related condition (2 variants)
• Cardiac arrhythmia (1 variants)
• Arrhythmogenic right ventricular cardiomyopathy (1 variants)
• Long QT syndrome 5, acquired, susceptibility to (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Long QT syndrome 2/5, digenic (1 variants)
• Jervell and Lange-Nielsen syndrome 1 (1 variants)
• Noise induced hearing loss (1 variants)
• Sudden unexplained death;Brugada syndrome;Arrhythmogenic right ventricular cardiomyopathy (1 variants)
• Hypertrophic cardiomyopathy (1 variants)
• SUDDEN INFANT DEATH SYNDROME (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNE1 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			1	44		45
missense	1	2	85	4	1	93
nonsense	1	2	1			4
start loss		1				1
frameshift	3	4	2			9
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1		3
non coding			42	31	33	106
Total	5	10	133	79	34

Variants in KCNE1

This is a list of pathogenic ClinVar variants found in the KCNE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-34446716-G-A		Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2 • Congenital long QT syndrome	Benign (Jan 13, 2018)
21-34446765-T-C		Congenital long QT syndrome • Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Benign (Jan 12, 2018)
21-34446770-T-C		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2;Long QT syndrome 5	Uncertain significance (Aug 30, 2021)
21-34446784-T-C		Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2 • Congenital long QT syndrome	Benign/Likely benign (Jan 13, 2018)
21-34446832-A-T		Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2 • Congenital long QT syndrome • Long QT syndrome 5;Jervell and Lange-Nielsen syndrome 2	Uncertain significance (Aug 17, 2021)
21-34446852-G-A		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Uncertain significance (Jan 13, 2018)
21-34446916-G-T		Jervell and Lange-Nielsen syndrome 2 • Congenital long QT syndrome • Long QT syndrome 5	Uncertain significance (Jan 12, 2018)
21-34446925-C-A		Congenital long QT syndrome • Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5;Jervell and Lange-Nielsen syndrome 2	Uncertain significance (Oct 06, 2021)
21-34446947-G-C		Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5;Jervell and Lange-Nielsen syndrome 2	Uncertain significance (Sep 30, 2021)
21-34447039-C-T		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Uncertain significance (Jan 13, 2018)
21-34447051-A-G		Congenital long QT syndrome • Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Likely benign (Jan 12, 2018)
21-34447095-C-T		Long QT syndrome 5 • Congenital long QT syndrome • Jervell and Lange-Nielsen syndrome 2	Likely benign (Jan 12, 2018)
21-34447122-C-T		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Benign/Likely benign (May 24, 2021)
21-34447142-G-A		Jervell and Lange-Nielsen syndrome 2 • Congenital long QT syndrome • Long QT syndrome 5	Benign/Likely benign (May 13, 2021)
21-34447147-A-G		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5 • Congenital long QT syndrome	Benign/Likely benign (May 13, 2021)
21-34447160-G-GTC			Likely benign (May 24, 2021)
21-34447237-C-T		Congenital long QT syndrome • Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Uncertain significance (Jan 13, 2018)
21-34447238-G-G		Congenital long QT syndrome • Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2	Benign (May 12, 2021)
21-34447244-C-T		Jervell and Lange-Nielsen syndrome 2 • Congenital long QT syndrome • Long QT syndrome 5	Conflicting classifications of pathogenicity (Jan 13, 2018)
21-34447245-G-A		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5 • Congenital long QT syndrome	Likely benign (Jan 13, 2018)
21-34447317-A-G		Congenital long QT syndrome • Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2	Uncertain significance (Jan 13, 2018)
21-34447386-C-T		Congenital long QT syndrome • Long QT syndrome 5 • Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5;Jervell and Lange-Nielsen syndrome 2	Uncertain significance (Jan 05, 2022)
21-34447388-C-T		Jervell and Lange-Nielsen syndrome 2 • Long QT syndrome 5	Uncertain significance (Jan 13, 2018)
21-34447407-A-T		Long QT syndrome 5 • Congenital long QT syndrome • Jervell and Lange-Nielsen syndrome 2	Likely benign (Jan 13, 2018)
21-34447413-G-A		Long QT syndrome 5 • Congenital long QT syndrome • Jervell and Lange-Nielsen syndrome 2	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNE1	protein_coding	protein_coding	ENST00000337385	1	65586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00340	0.400	125730	0	6	125736	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.616	97	81.4	1.19	0.00000536	837
Missense in Polyphen		24	25.367	0.9461		291
Synonymous	-1.39	48	37.2	1.29	0.00000279	267
Loss of Function	-0.634	3	2.03	1.48	8.72e-8	22

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:19219384). Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr). {ECO:0000269|PubMed:19219384}.
• Disease: DISEASE: Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347]: 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:10400998, ECO:0000269|PubMed:21676880, ECO:0000269|PubMed:9328483, ECO:0000269|PubMed:9354783}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Long QT syndrome 5 (LQT5) [MIM:613695]: 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:10400998, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11692163, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:9354802, ECO:0000269|PubMed:9445165}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adrenergic signaling in cardiomyocytes - Homo sapiens (human);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;Phase 2 - plateau phase;Phase 3 - rapid repolarisation;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.333

Intolerance Scores

• loftool: 0.0168
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.53

Haploinsufficiency Scores

• pHI: 0.116
• hipred: N
• hipred_score: 0.396
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.814

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcne1
• Phenotype: hematopoietic system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); digestive/alimentary phenotype; hearing/vestibular/ear 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: sensory perception of sound;regulation of ventricular cardiac muscle cell membrane repolarization;cellular response to cAMP;potassium ion transmembrane transport;cardiac muscle cell action potential involved in contraction;ventricular cardiac muscle cell action potential;membrane repolarization;membrane repolarization during action potential;membrane repolarization during cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;negative regulation of protein targeting to membrane;potassium ion export across plasma membrane;membrane repolarization during ventricular cardiac muscle cell action potential;regulation of potassium ion transmembrane transport;positive regulation of potassium ion transmembrane transport;regulation of delayed rectifier potassium channel activity;negative regulation of delayed rectifier potassium channel activity
• Cellular component: lysosome;plasma membrane;voltage-gated potassium channel complex;cell surface;apical plasma membrane;Z disc;membrane raft
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;potassium channel regulator activity;telethonin binding;ion channel binding;voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization