KCND3
potassium voltage-gated channel subfamily D member 3, the group of Potassium voltage-gated channels
Basic information
Region (hg38): 1:111770662-111989668
Previous symbols: [ "SCA22", "SCA19" ]
Links
Phenotypes
GenCC
Source:
- Brugada syndrome 9 (Limited), mode of inheritance: AD
- spinocerebellar ataxia type 19/22 (Strong), mode of inheritance: AD
- spinocerebellar ataxia type 19/22 (Supportive), mode of inheritance: AD
- spinocerebellar ataxia type 19/22 (Strong), mode of inheritance: AD
- spinocerebellar ataxia type 19/22 (Strong), mode of inheritance: AD
- Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD
- neurodevelopmental disorder (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Brugada syndrome 9 | AD | Cardiovascular | Individuals have been described as manifesting with arrhythmias and sudden cardiac death, and early diagnosis may allow management (such as with ICD placement) | Cardiovascular; Neurologic | 21349352; 22457051; 23280837; 23280838 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cardiovascular_phenotype (376 variants)
- Spinocerebellar_ataxia_type_19/22 (315 variants)
- not_provided (166 variants)
- not_specified (49 variants)
- Brugada_syndrome_9 (24 variants)
- KCND3-related_disorder (12 variants)
- Variant_of_unknown_significance (2 variants)
- Neurodevelopmental_delay (2 variants)
- Hereditary_ataxia (2 variants)
- Brugada_syndrome (2 variants)
- Epilepsy (1 variants)
- Intellectual_disability (1 variants)
- Inborn_genetic_diseases (1 variants)
- Primary_dilated_cardiomyopathy (1 variants)
- Seizure (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCND3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001378969.1. 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 | 247 | 254 | ||||
| missense | 10 | 22 | 265 | 19 | 317 | |
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 10 | 23 | 273 | 266 | 6 |
Highest pathogenic variant AF is 0.000013010653
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KCND3 | protein_coding | protein_coding | ENST00000315987 | 7 | 218494 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.990 | 0.0103 | 125740 | 0 | 6 | 125746 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.85 | 209 | 435 | 0.480 | 0.0000322 | 4293 |
| Missense in Polyphen | 7 | 43.252 | 0.16184 | 360 | ||
| Synonymous | 0.550 | 182 | 192 | 0.949 | 0.0000156 | 1343 |
| Loss of Function | 4.01 | 2 | 22.6 | 0.0886 | 0.00000109 | 251 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000578 | 0.0000578 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits. {ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:9843794}.;
- Disease
- DISEASE: Spinocerebellar ataxia 19 (SCA19) [MIM:607346]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis. {ECO:0000269|PubMed:23280837, ECO:0000269|PubMed:23280838, ECO:0000269|PubMed:28895081}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brugada syndrome 9 (BRGDA9) [MIM:616399]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:21349352, ECO:0000269|PubMed:22457051}. Note=The gene represented in this entry may be involved in disease pathogenesis.;
- 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;Phase 1 - inactivation of fast Na+ channels;Cardiac conduction;Muscle contraction;Voltage gated Potassium channels;Potassium Channels
(Consensus)
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- loftool
- 0.0288
- rvis_EVS
- -0.8
- rvis_percentile_EVS
- 12.24
Haploinsufficiency Scores
- pHI
- 0.375
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.705
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.370
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kcnd3
- Phenotype
Gene ontology
- Biological process
- potassium ion transport;regulation of ion transmembrane transport;protein homooligomerization;potassium ion transmembrane transport;membrane repolarization;membrane repolarization during cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;potassium ion export across plasma membrane;membrane repolarization during ventricular cardiac muscle cell action potential;ventricular cardiac muscle cell membrane repolarization
- Cellular component
- plasma membrane;voltage-gated potassium channel complex;integral component of membrane;dendrite;sarcolemma;neuronal cell body;GABA-ergic synapse;integral component of postsynaptic specialization membrane
- Molecular function
- voltage-gated potassium channel activity;A-type (transient outward) potassium channel activity;protein binding;ion channel binding;metal ion 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