KCNJ2
potassium inwardly rectifying channel subfamily J member 2, the group of Potassium inwardly rectifying channel subfamily J
Basic information
Region (hg38): 17:70168673-70180044
Links
Phenotypes
GenCC
Source:
- catecholaminergic polymorphic ventricular tachycardia (Limited), mode of inheritance: AD
- Andersen-Tawil syndrome (Strong), mode of inheritance: AD
- familial atrial fibrillation (Supportive), mode of inheritance: AD
- Andersen-Tawil syndrome (Supportive), mode of inheritance: AD
- short QT syndrome (Supportive), mode of inheritance: AD
- short QT syndrome type 3 (Moderate), mode of inheritance: AD
- Andersen-Tawil syndrome (Definitive), mode of inheritance: AD
- short QT syndrome type 3 (Strong), mode of inheritance: AD
- Andersen-Tawil syndrome (Strong), mode of inheritance: AD
- long QT syndrome (Limited), mode of inheritance: AD
- short QT syndrome (Moderate), mode of inheritance: AD
- catecholaminergic polymorphic ventricular tachycardia (Disputed Evidence), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Atrial fibrillation, familial 9; Short QT syndrome 3; Andersen syndrome; Long QT syndrome 7 | AD | Cardiovascular | Depending on the cardiac phenotype, specific medical intervention to prevent morbidity and mortality related to arrhythmias can be beneficial; Surveillance for cardiac events is indicated | Cardiovascular; Musculoskeletal | 4106724; 5007210; 8080508; 9307251; 10406668; 11371347; 12148092; 12177393; 12086641; 12163457; 12796536; 15761194; 15890322; 16217063; 15922306; 16571646; 16419128; 16769944; 17324964; 17211524; 19931173; 20111058; 20301441; 20382953; 20809527; 21148745; 21493816; 21875779; 22155372; 22589293 |
ClinVar
This is a list of variants' phenotypes submitted to
- Andersen Tawil syndrome;Short QT syndrome type 3 (19 variants)
- Congenital long QT syndrome (17 variants)
- Andersen Tawil syndrome (11 variants)
- not provided (10 variants)
- Short QT syndrome type 3;Andersen Tawil syndrome (4 variants)
- Cardiovascular phenotype (3 variants)
- Andersen Tawil syndrome;Atrial fibrillation, familial, 9;Short QT syndrome type 3 (2 variants)
- Short QT syndrome type 3 (2 variants)
- not specified (1 variants)
- Atrial fibrillation, familial, 9;Andersen Tawil syndrome;Short QT syndrome type 3 (1 variants)
- Ventricular tachycardia (1 variants)
- Supraventricular tachycardia (1 variants)
- Short QT syndrome (1 variants)
- Andersen Tawil syndrome;Short QT syndrome type 1;Atrial fibrillation, familial, 1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ2 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 | 125 | 127 | ||||
| missense | 22 | 22 | 193 | 239 | ||
| nonsense | 9 | |||||
| start loss | 2 | |||||
| frameshift | 3 | |||||
| inframe indel | 8 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 68 | 14 | 22 | 104 | ||
| Total | 28 | 24 | 275 | 140 | 25 |
Highest pathogenic variant AF is 0.00000657
Variants in KCNJ2
This is a list of pathogenic ClinVar variants found in the KCNJ2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCNJ2 | protein_coding | protein_coding | ENST00000243457 | 1 | 11376 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.307 | 0.690 | 125730 | 0 | 5 | 125735 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.75 | 121 | 241 | 0.502 | 0.0000153 | 2845 |
| Missense in Polyphen | 24 | 119.1 | 0.2015 | 1390 | ||
| Synonymous | -0.945 | 104 | 92.4 | 1.13 | 0.00000640 | 830 |
| Loss of Function | 2.51 | 3 | 12.6 | 0.238 | 8.87e-7 | 142 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium or cesium.;
- Disease
- DISEASE: Long QT syndrome 7 (LQT7) [MIM:170390]: 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. Long QT syndrome type 7 manifests itself as a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy and dysmorphic features. {ECO:0000269|PubMed:11371347, ECO:0000269|PubMed:12148092, ECO:0000269|PubMed:12163457, ECO:0000269|PubMed:16571646, ECO:0000269|PubMed:17324964}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Short QT syndrome 3 (SQT3) [MIM:609622]: 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. SQT3 has a unique ECG phenotype characterized by asymmetrical T waves. {ECO:0000269|PubMed:15761194}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrial fibrillation, familial, 9 (ATFB9) [MIM:613980]: 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:15922306}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Oxytocin signaling pathway - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Renin secretion - Homo sapiens (human);Cholinergic synapse - 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;miR-targeted genes in epithelium - TarBase;Pathways in clear cell renal cell carcinoma;Neuronal System;Phase 4 - resting membrane potential;Cardiac conduction;Muscle contraction;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Activation of GABAB receptors;GABA B receptor activation;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Activation of G protein gated Potassium channels;Classical Kir channels;G protein gated Potassium channels;Inwardly rectifying K+ channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.221
Intolerance Scores
- loftool
- 0.0226
- rvis_EVS
- -0.58
- rvis_percentile_EVS
- 18.44
Haploinsufficiency Scores
- pHI
- 0.429
- hipred
- Y
- hipred_score
- 0.749
- ghis
- 0.560
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.797
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcnj2
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; muscle phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- potassium ion transport;regulation of skeletal muscle contraction via regulation of action potential;magnesium ion transport;cellular potassium ion homeostasis;protein homotetramerization;relaxation of cardiac muscle;regulation of resting membrane potential;regulation of membrane repolarization;cellular response to mechanical stimulus;potassium ion transmembrane transport;cardiac muscle cell action potential involved in contraction;regulation of cardiac muscle cell contraction;membrane repolarization during action potential;membrane depolarization during cardiac muscle cell action potential;membrane repolarization during cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;relaxation of skeletal muscle;positive regulation of potassium ion transmembrane transport;potassium ion import across plasma membrane
- Cellular component
- smooth endoplasmic reticulum;rough endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;intercalated disc;T-tubule;intrinsic component of membrane;neuronal cell body;dendritic spine
- Molecular function
- inward rectifier potassium channel activity;phosphatidylinositol-4,5-bisphosphate binding;G-protein activated inward rectifier potassium channel activity;identical protein binding;voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization