KCND3: Potassium Voltage-Gated Channel Subfamily D Member 3
A key regulator of cardiac and neuronal excitability, associated with Brugada syndrome and neurodevelopmental disorders.
Gene Information Card
| Symbol | KCND3 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily D Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 3752 ncbi.nlm.nih.gov/gene/3752 |
| Ensembl ID | ENSG00000171385 |
| UniProt ID | Q9UK17 |
| OMIM ID | 605411 |
| HGNC ID | 6239 |
| Aliases | Kv4.3, KSHIVB, SCA19, SCA22 |
Description
KCND3 encodes the Kv4.3 voltage-gated potassium channel, which mediates the transient outward potassium current (I_to) in cardiac myocytes and regulates neuronal excitability. Mutations in KCND3 are linked to Brugada syndrome (cardiac arrhythmia) and spinocerebellar ataxia types 19 and 22 (neurodegenerative disorders).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brugada syndrome | Loss-of-function mutations reduce I_to current, predisposing to ventricular fibrillation | ClinVar, OMIM |
| Spinocerebellar ataxia 19 (SCA19) | Dominant-negative or gain-of-function effects impair cerebellar Purkinje cell firing | OMIM, PubMed |
| Spinocerebellar ataxia 22 (SCA22) | Allelic variant of SCA19 with similar mechanism | OMIM |
| Early infantile epileptic encephalopathy | Rare de novo missense variants alter channel gating | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 28.5 | High |
| Brain (cerebellum) | 22.1 | High |
| Skeletal muscle | 10.3 | Medium |
| Pancreas | 6.7 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 32.0 | High expression |
| SH-SY5Y (neuroblastoma) | 18.5 | Moderate |
| HEK293 | 0.8 | Low/transient |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003G>A (p.Gly335Arg) | Missense | <0.01% | Loss-of-function; Brugada syndrome |
| c.1169C>T (p.Thr390Met) | Missense | <0.01% | Gain-of-function; SCA19 |
| c.1378G>A (p.Glu460Lys) | Missense | <0.01% | Dominant-negative; SCA22 |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss-of-function; Brugada syndrome |
Mutation functional classification
Loss of Function (LOF)
Reduced I_to current density; associated with Brugada syndrome (e.g., p.Gly335Arg).
Gain of Function (GOF)
Increased channel activity or altered inactivation; linked to SCA19 (e.g., p.Thr390Met).
Dominant Negative (DN)
Mutant subunits impair wild-type channel function; observed in SCA22 (e.g., p.Glu460Lys).
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac conduction (Reactome: R-HSA-5576891)
• Voltage gated potassium channels (KEGG: hsa04010)
• Transient outward potassium current (I_to) (PW:0000802)
Protein Summary
Kv4.3 is a pore-forming alpha subunit of voltage-gated potassium channels. It assembles as a tetramer to form the I_to channel in cardiac muscle and mediates A-type potassium currents in neurons. The protein contains six transmembrane domains (S1-S6) with a voltage-sensor in S4 and a pore loop between S5 and S6. Post-translational modifications include N-glycosylation and phosphorylation, which modulate channel trafficking and kinetics.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCND3 Knockout HEK293 Cell Line | EDJ-KQ5023 | Human | 3752 | Details Get a Quote |
| KCND3 Knockout HeLa Cell Line | EDJ-KQ53706 | Human | 3752 | Details Get a Quote |
| KCND3 Knockout A-549 Cell Line | EDJ-KQ62184 | Human | 3752 | Details Get a Quote |
| KCND3 Knockout HCT 116 Cell Line | EDJ-KQ70669 | Human | 3752 | Details Get a Quote |
