KCNA3: Potassium Voltage-Gated Channel Subfamily A Member 3
Key regulator of immune cell function and neuronal excitability
Gene Information Card
| Symbol | KCNA3 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily A Member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 3738 ncbi.nlm.nih.gov/gene/3738 |
| Ensembl ID | ENSG00000177272 |
| UniProt ID | P22001 |
| OMIM ID | 176263 |
| HGNC ID | 6221 |
| Aliases | Kv1.3, HPCN3, MK3, HLK3 |
Description
KCNA3 encodes the voltage-gated potassium channel Kv1.3, a Shaker-related channel predominantly expressed in lymphocytes and the nervous system. It mediates the delayed rectifier current (IKv1.3) essential for T-cell activation, proliferation, and calcium signaling. The channel is a target for immunomodulation in autoimmune diseases and cancer immunotherapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple sclerosis | Kv1.3 overexpression in activated T-cells enhances calcium influx and pro-inflammatory cytokine release | PMID: 23467322 |
| Type 1 diabetes | Kv1.3 blockade reduces autoreactive T-cell responses in pancreatic islets | PMID: 19047651 |
| Rheumatoid arthritis | Increased Kv1.3 expression in synovial T-cells correlates with disease activity | PMID: 21813794 |
| Psoriasis | Kv1.3 inhibition attenuates T-cell-mediated skin inflammation | PMID: 25231990 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Thymus | 8.2 | Medium |
| Cerebral cortex | 6.1 | Low |
| Cerebellum | 5.4 | Low |
| Bone marrow | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat T-cells | 15.2 | High expression |
| Raji B-cells | 3.1 | Low expression |
| HEK293 | 0.8 | Very low expression |
| SH-SY5Y | 7.6 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1009G>A (p.Gly337Ser) | Missense | <0.01% | Reduced channel conductance |
| c.1124C>T (p.Thr375Met) | Missense | <0.01% | Altered voltage dependence |
| c.1283A>G (p.Asn428Ser) | Missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
p.Gly337Ser reduces potassium current amplitude by ~40% in heterologous expression systems.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in KCNA3.
Dominant Negative (DN)
p.Thr375Met may exert dominant-negative effects when co-expressed with wild-type subunits.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG hsa04010: MAPK signaling pathway
• KEGG hsa04660: T cell receptor signaling pathway
• Reactome R-HSA-1296072: Voltage gated potassium channels
• Reactome R-HSA-388844: Regulation of T cell activation
Protein Summary
Kv1.3 (KCNA3) is a 575-amino acid voltage-gated potassium channel with six transmembrane segments (S1-S6) and a pore-forming loop. It assembles as homotetramers or heterotetramers with other Kv1 family members. The channel is highly expressed in effector memory T-cells, where it regulates membrane potential and calcium signaling. Pharmacological blockers (e.g., ShK-186, dalazatide) are in clinical trials for autoimmune diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNA3 Knockout HEK293 Cell Line | EDJ-KQ5033 | Human | 3738 | Details Get a Quote |
| KCNA3 Knockout HeLa Cell Line | EDJ-KQ53694 | Human | 3738 | Details Get a Quote |
| KCNA3 Knockout A-549 Cell Line | EDJ-KQ62172 | Human | 3738 | Details Get a Quote |
| KCNA3 Knockout HCT 116 Cell Line | EDJ-KQ70658 | Human | 3738 | Details Get a Quote |
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