KCNA5
potassium voltage-gated channel subfamily A member 5, the group of Potassium voltage-gated channels
Basic information
Region (hg38): 12:5043879-5046788
Links
Phenotypes
GenCC
Source:
- atrial fibrillation, familial, 7 (Moderate), mode of inheritance: AD
- familial atrial fibrillation (Supportive), mode of inheritance: AD
- atrial fibrillation, familial, 7 (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Atrial fibrillation, familial, 7 | AD | Cardiovascular | Surveillance for and medical intervention to prevent morbidity related to atrial fibrillation may be beneficial | Cardiovascular | 16772329; 17266934; 19343045; 20638934 |
ClinVar
This is a list of variants' phenotypes submitted to
- Atrial_fibrillation,_familial,_7 (455 variants)
- not_provided (92 variants)
- Inborn_genetic_diseases (74 variants)
- not_specified (17 variants)
- KCNA5-related_disorder (13 variants)
- Pulmonary_arterial_hypertension (5 variants)
- Brugada_syndrome_1 (1 variants)
- altered_potassium_channel_function (1 variants)
- Pulmonary_hypertension,_primary,_1 (1 variants)
- Third_degree_atrioventricular_block (1 variants)
- Heart_disease (1 variants)
- Cardiac_arrhythmia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNA5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002234.4. 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 | 23 | 114 | 143 | |||
| missense | 316 | 25 | 346 | |||
| nonsense | 6 | |||||
| start loss | 2 | 2 | ||||
| frameshift | 14 | 14 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 2 | 359 | 139 | 8 |
Highest pathogenic variant AF is 0.000010533
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCNA5 | protein_coding | protein_coding | ENST00000252321 | 1 | 2865 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00109 | 0.956 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.0540 | 401 | 398 | 1.01 | 0.0000274 | 3936 |
| Missense in Polyphen | 167 | 187.7 | 0.88971 | 1883 | ||
| Synonymous | -1.58 | 207 | 180 | 1.15 | 0.0000132 | 1342 |
| Loss of Function | 1.79 | 7 | 14.3 | 0.489 | 7.99e-7 | 147 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:8505626, PubMed:12130714). May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation (PubMed:11524461). {ECO:0000269|PubMed:11524461, ECO:0000269|PubMed:12130714, ECO:0000269|PubMed:8505626}.;
- Disease
- DISEASE: Atrial fibrillation, familial, 7 (ATFB7) [MIM:612240]: A familial 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:16772329}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- 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;Neuronal System;Voltage gated Potassium channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.206
Intolerance Scores
- loftool
- 0.0940
- rvis_EVS
- 0.8
- rvis_percentile_EVS
- 87.59
Haploinsufficiency Scores
- pHI
- 0.240
- hipred
- Y
- hipred_score
- 0.540
- ghis
- 0.425
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.843
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcna5
- 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); hematopoietic system phenotype; immune system 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); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- response to hypoxia;potassium ion transport;Notch signaling pathway;response to mechanical stimulus;response to organic substance;regulation of vasoconstriction;regulation of membrane potential;response to hydrogen peroxide;regulation of potassium ion transport;regulation of insulin secretion;protein homooligomerization;negative regulation of cytosolic calcium ion concentration;potassium ion homeostasis;response to hyperoxia;membrane hyperpolarization;regulation of atrial cardiac muscle cell membrane repolarization;potassium ion transmembrane transport;atrial cardiac muscle cell action potential;membrane repolarization during bundle of His cell action potential;membrane repolarization during SA node 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;positive regulation of G1/S transition of mitotic cell cycle;positive regulation of myoblast proliferation
- Cellular component
- endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;caveola;voltage-gated potassium channel complex;cell surface;intercalated disc;integral component of membrane;Z disc;potassium channel complex;membrane raft;intracellular canaliculus;perinuclear region of cytoplasm
- Molecular function
- signaling receptor binding;voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;outward rectifier potassium channel activity;protein kinase binding;alpha-actinin binding;voltage-gated potassium channel activity involved in bundle of His cell action potential repolarization;voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in SA node cell action potential repolarization;scaffold protein binding