KCNJ5
potassium inwardly rectifying channel subfamily J member 5, the group of Potassium inwardly rectifying channel subfamily J
Basic information
Region (hg38): 11:128891356-128921163
Links
Phenotypes
GenCC
Source:
- Andersen-Tawil syndrome (Supportive), mode of inheritance: AD
- familial hyperaldosteronism type III (Supportive), mode of inheritance: AD
- familial hyperaldosteronism type III (Strong), mode of inheritance: AD
- long QT syndrome 13 (Limited), mode of inheritance: AD
- long QT syndrome (Disputed Evidence), mode of inheritance: AD
- long QT syndrome 13 (Limited), mode of inheritance: AD
- familial hyperaldosteronism type III (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Long QT syndrome 13; Hyperaldosteronism, familial, type III | AD | Cardiovascular; Endocrine | In Long QT syndrome, preventive measures and medical management may be helpful to help decrease morbidity; sudden death in infancy has been reported; In Hyperaldosteronism, familial, hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy | Cardiovascular; Endocrine | 18505761; 20301308; 20560207; 21311022; 22447138; 22628607; 24574546 |
ClinVar
This is a list of variants' phenotypes submitted to
- Long_QT_syndrome (236 variants)
- Cardiovascular_phenotype (220 variants)
- Familial_hyperaldosteronism_type_III (91 variants)
- not_provided (79 variants)
- Long_QT_syndrome_13 (74 variants)
- not_specified (24 variants)
- KCNJ5-related_disorder (15 variants)
- Congenital_long_QT_syndrome (10 variants)
- Aldosterone-producing_adrenal_adenoma,_somatic (2 variants)
- Hypertrophic_cardiomyopathy (2 variants)
- Andersen_Tawil_syndrome (2 variants)
- Familial_hyperaldosteronism (1 variants)
- See_cases (1 variants)
- Primary_dilated_cardiomyopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNJ5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000890.5. 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 | 126 | 130 | ||||
| missense | 195 | 26 | 230 | |||
| nonsense | 8 | |||||
| start loss | 0 | |||||
| frameshift | 8 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 3 | 214 | 153 | 1 |
Highest pathogenic variant AF is 0.000004800643
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCNJ5 | protein_coding | protein_coding | ENST00000529694 | 2 | 29680 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000336 | 0.834 | 125727 | 0 | 21 | 125748 | 0.0000835 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.33 | 190 | 249 | 0.763 | 0.0000162 | 2777 |
| Missense in Polyphen | 92 | 124.85 | 0.73686 | 1338 | ||
| Synonymous | -0.388 | 104 | 99.1 | 1.05 | 0.00000663 | 828 |
| Loss of Function | 1.23 | 7 | 11.5 | 0.608 | 6.93e-7 | 125 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000206 | 0.000206 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.0000933 | 0.0000924 |
| European (Non-Finnish) | 0.0000616 | 0.0000615 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: This potassium channel is controlled by G proteins. 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 external barium. {ECO:0000269|PubMed:22315453, ECO:0000269|PubMed:22628607, ECO:0000269|PubMed:24037882, ECO:0000269|PubMed:27099398, ECO:0000269|PubMed:27293068}.;
- Disease
- DISEASE: Hyperaldosteronism, familial, 3 (HALD3) [MIM:613677]: A form of hyperaldosteronism characterized by hypertension secondary to massive adrenal mineralocorticoid production. HALD3 patients present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. Hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension. {ECO:0000269|PubMed:21311022, ECO:0000269|PubMed:22203740, ECO:0000269|PubMed:22275527, ECO:0000269|PubMed:22308486, ECO:0000269|PubMed:22315453, ECO:0000269|PubMed:22628607, ECO:0000269|PubMed:22848660, ECO:0000269|PubMed:24037882, ECO:0000269|PubMed:27099398}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Somatic mutations in KCNJ5 have been found in aldosterone-producing adrenal adenomas and can be responsible for aldosteronism associated with cell autonomous proliferation. APAs are typically solitary, well circumscribed tumors diagnosed between ages 30 and 70. They come to medical attention due to new or worsening hypertension, often with hypokalemia. The precise role of KCNJ5 mutations in APA is under debate. They produce increased sodium conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium entry, the signal for aldosterone production and cell proliferation. However, they may not be causative of APA development but may be a consequence of tumorigenesis, playing only a contributory role toward aldosterone overproduction and tumor growth (PubMed:22275527). Somatic mutations in KCNJ5 have not been found in non-aldosterone secreting adrenal adenomas suggesting that they are specifically associated with APA (PubMed:22275527 and PubMed:22848660). {ECO:0000269|PubMed:21311022, ECO:0000269|PubMed:22203740, ECO:0000269|PubMed:22275527, ECO:0000269|PubMed:22848660}.; DISEASE: Note=Mutations in KCNJ5 are involved in the pathogenesis of hypertension without primary aldosteronism but with increased aldosterone response to ACTH stimulation. {ECO:0000269|PubMed:27293068}.;
- Pathway
- Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Morphine addiction - 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;Notch Signaling Pathway;Notch Signaling Pathway;Calcium Regulation in the Cardiac Cell;Neuronal System;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;G protein gated Potassium channels;Inwardly rectifying K+ channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- loftool
- 0.101
- rvis_EVS
- -0.53
- rvis_percentile_EVS
- 20.7
Haploinsufficiency Scores
- pHI
- 0.146
- hipred
- Y
- hipred_score
- 0.651
- ghis
- 0.585
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.372
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcnj5
- 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);
Gene ontology
- Biological process
- potassium ion transport;regulation of ion transmembrane transport;regulation of heart rate by cardiac conduction;membrane repolarization during atrial cardiac muscle cell action potential;membrane repolarization during ventricular cardiac muscle cell action potential;ventricular cardiac muscle cell membrane repolarization;potassium ion import across plasma membrane
- Cellular component
- plasma membrane;voltage-gated potassium channel complex;external side of plasma membrane;T-tubule
- Molecular function
- inward rectifier potassium channel activity;protein binding;G-protein activated inward rectifier potassium channel activity;voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization