KCNE3
potassium voltage-gated channel subfamily E regulatory subunit 3, the group of Potassium voltage-gated channel regulatory subunits
Basic information
Region (hg38): 11:74454841-74467729
Links
Phenotypes
GenCC
Source:
- Brugada syndrome 6 (Limited), mode of inheritance: Unknown
- Brugada syndrome 6 (Disputed Evidence), mode of inheritance: AD
- Brugada syndrome 6 (Disputed Evidence), mode of inheritance: Unknown
- Brugada syndrome 6 (Limited), mode of inheritance: AD
- Brugada syndrome (Disputed Evidence), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Brugada syndrome 6 | AD | Cardiovascular; Pharmacogenomic | Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever | Cardiovascular | 12414843; 14504341; 15037716; 15212652; 19122847; 19306396; 19606473; 20301690; 22397033; 22987075 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cardiovascular_phenotype (75 variants)
- Brugada_syndrome_6 (63 variants)
- not_provided (11 variants)
- not_specified (10 variants)
- Encephalopathy,_neonatal_severe,_with_lactic_acidosis_and_brain_abnormalities (2 variants)
- KCNE3-related_disorder (2 variants)
- Long_QT_syndrome (2 variants)
- Prolonged_QT_interval (2 variants)
- Cardiomyopathy (1 variants)
- Ventricular_fibrillation (1 variants)
- Syncope (1 variants)
- Periodic_paralysis (1 variants)
- Brugada_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNE3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005472.5. 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 | 18 | 19 | ||||
| missense | 55 | 15 | 70 | |||
| nonsense | 1 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 61 | 34 | 1 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCNE3 | protein_coding | protein_coding | ENST00000310128 | 1 | 12889 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.468 | 0.450 | 125695 | 0 | 8 | 125703 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.238 | 62 | 67.5 | 0.918 | 0.00000422 | 668 |
| Missense in Polyphen | 19 | 23.551 | 0.80676 | 256 | ||
| Synonymous | 0.548 | 21 | 24.4 | 0.859 | 0.00000123 | 218 |
| Loss of Function | 1.19 | 0 | 1.65 | 0.00 | 6.88e-8 | 23 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000431 | 0.000431 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| 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:12954870). Associated with KCNC4/Kv3.4 is proposed to form the subthreshold voltage-gated potassium channel in skeletal muscle and to establish the resting membrane potential (RMP) in muscle cells. Associated with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion that produces a current with nearly instantaneous activation with a linear current-voltage relationship. {ECO:0000250|UniProtKB:Q9JJV7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:12954870}.;
- Pathway
- Protein digestion and absorption - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;TYROBP Causal Network;Phase 2 - plateau phase;Phase 3 - rapid repolarisation;Cardiac conduction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- loftool
- 0.219
- rvis_EVS
- 0.19
- rvis_percentile_EVS
- 66.57
Haploinsufficiency Scores
- pHI
- 0.132
- hipred
- N
- hipred_score
- 0.310
- ghis
- 0.515
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.821
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcne3
- 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); digestive/alimentary phenotype; immune system phenotype; respiratory 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); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- regulation of ventricular cardiac muscle cell membrane repolarization;ventricular cardiac muscle cell action potential;membrane repolarization during action potential;regulation of heart rate by cardiac conduction;potassium ion export across plasma membrane;membrane repolarization during ventricular cardiac muscle cell action potential;positive regulation of voltage-gated calcium channel activity;negative regulation of delayed rectifier potassium channel activity;negative regulation of potassium ion export across plasma membrane;negative regulation of voltage-gated potassium channel activity;negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential
- Cellular component
- cytoplasm;plasma membrane;voltage-gated potassium channel complex;dendrite;vesicle;neuronal cell body membrane;perikaryon;membrane raft
- Molecular function
- delayed rectifier potassium channel activity;protein binding;potassium channel regulator activity;ion channel binding;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization