KCNE1
potassium voltage-gated channel subfamily E regulatory subunit 1, the group of Potassium voltage-gated channel regulatory subunits
Basic information
Region (hg38): 21:34446688-34512214
Links
Phenotypes
GenCC
Source:
- 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
- atrial fibrillation (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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
- Long_QT_syndrome (170 variants)
- Cardiovascular_phenotype (117 variants)
- not_provided (104 variants)
- Jervell_and_Lange-Nielsen_syndrome_2 (51 variants)
- Long_QT_syndrome_5 (51 variants)
- not_specified (45 variants)
- Congenital_long_QT_syndrome (34 variants)
- KCNE1-related_disorder (6 variants)
- Cardiomyopathy (3 variants)
- Jervell_and_Lange-Nielsen_syndrome_1 (2 variants)
- Arrhythmogenic_right_ventricular_cardiomyopathy (2 variants)
- Rare_genetic_deafness (1 variants)
- Jervell_and_Lange-Nielsen_syndrome (1 variants)
- Hereditary_hearing_loss_and_deafness (1 variants)
- Long_QT_syndrome_5,_acquired,_susceptibility_to (1 variants)
- Hypertrophic_cardiomyopathy (1 variants)
- Cardiac_arrhythmia (1 variants)
- Primary_dilated_cardiomyopathy (1 variants)
- SUDDEN_INFANT_DEATH_SYNDROME (1 variants)
- Long_QT_syndrome_2/5,_digenic (1 variants)
- Sensorineural_hearing_loss_disorder (1 variants)
- Noise_induced_hearing_loss (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. These statistics are base on transcript: NM_000000219.6. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 188 | 59 | 247 | |||
| missense | 791 | 16 | 821 | |||
| nonsense | 38 | 43 | ||||
| start loss | 1 | 8 | 9 | |||
| frameshift | 13 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 12 | 13 | 1030 | 75 | 4 |
Highest pathogenic variant AF is 0.00433362
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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