KCNA3
protein-codingpotassium voltage-gated channel subfamily A member 3, the group of Potassium voltage-gated channels
Gene summary
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KCNA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002232.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 16 | 89 | 4 | 2 | 111 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 16 | 90 | 9 | 3 | 118 |
Highest pathogenic variant AF is 0.0000020521352
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002223.3 | 1 | MANE Select | |
| Ensembl | ENSP00000358784.2 | 1 | MANE Select | |
| Ensembl | ENSP00000513296.1 | 1 | Standard | |
| Ensembl | ENSP00000513297.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
- Neuronal System
- BDNF
- Voltage gated Potassium channels
- Potassium Channels
Biological Process
- potassium ion transport
- regulation of ion transmembrane transport
- protein homooligomerization
- potassium ion transmembrane transport
- potassium ion export across plasma membrane
Molecular Function
- voltage-gated ion channel activity
- voltage-gated potassium channel activity
- delayed rectifier potassium channel activity
- protein binding
- outward rectifier potassium channel activity
Cellular Component
- plasma membrane
- voltage-gated potassium channel complex
- integral component of membrane
- axon
- calyx of Held
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369769
- Coding exons
- 1
- Length
- 3346
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.02 | 194 | 354 | 0.549 | 0.0000215 | 3719 |
| Missense (PolyPhen) | 43 | 158.43 | 0.27141 | 1635 | ||
| Synonymous | 1.18 | 145 | 164 | 0.883 | 0.0000110 | 1230 |
| Loss of Function | 3.25 | 2 | 16.1 | 0.124 | 9.64e-7 | 154 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.;
Recessive Scores
- pRec
- 0.228
Intolerance Scores
- LoFtool
- 0.235
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 67.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.676
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |