KCNIP2: Kv Channel Interacting Protein 2
A key regulator of voltage-gated potassium channels in cardiac and neuronal tissues
Gene Information Card
| Symbol | KCNIP2 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Interacting Protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 30819 ncbi.nlm.nih.gov/gene/30819 |
| Ensembl ID | ENSG00000120049 |
| UniProt ID | Q9NS61 |
| OMIM ID | 604604 |
| HGNC ID | 6282 |
| Aliases | KChIP2, KCNIP2A, KCNIP2B, KCNIP2C |
Description
KCNIP2 encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KChIPs). This protein binds to the N-terminus of Kv4 alpha subunits, modulating their surface expression, gating kinetics, and inactivation properties. KCNIP2 is highly expressed in the heart and brain, playing a critical role in cardiac repolarization and neuronal excitability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac arrhythmia (e.g., Brugada syndrome, long QT syndrome) | Altered Kv4 channel function due to KCNIP2 variants disrupts cardiac repolarization, increasing arrhythmia risk. | ClinVar, OMIM |
| Epilepsy | Dysregulation of Kv4 channels in neurons may contribute to hyperexcitability and seizure susceptibility. | NCBI Gene, literature |
| Atrial fibrillation | Reduced KCNIP2 expression in atrial tissue is associated with electrical remodeling and fibrillation. | PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Brain | 28.7 | Medium |
| Skeletal muscle | 12.3 | Low |
| Pancreas | 8.1 | Low |
| Liver | 2.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 52.0 | High expression |
| SH-SY5Y (neuronal) | 30.5 | Moderate expression |
| HEK293 | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.458C>T (p.Pro153Leu) | Missense | <0.01% | Reduced Kv4.3 current density; associated with Brugada syndrome (ClinVar) |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; linked to long QT syndrome (ClinVar) |
| c.682G>A (p.Glu228Lys) | Missense | <0.01% | Altered channel inactivation; reported in epilepsy (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
p.Met1Val and p.Pro153Leu reduce or abolish KCNIP2 protein function, impairing Kv4 channel trafficking and current.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
p.Pro153Leu may exert dominant-negative effects by interfering with wild-type KCNIP2 binding to Kv4 subunits.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated ion channel activity (GO:0005244) | • protein binding (GO:0005515) |
| • potassium channel regulator activity (GO:0015459) | • axon (GO:0030424) |
| • neuronal cell body (GO:0043025) | • potassium ion transmembrane transport (GO:0071805) |
Pathways
• Kv4-mediated potassium channel regulation (Reactome: R-HSA-1296072)
• Cardiac conduction (KEGG: hsa05414)
• Neuronal system (KEGG: hsa04728)
Protein Summary
KCNIP2 (KChIP2) is a 270-amino acid protein containing four EF-hand calcium-binding domains. It forms a complex with Kv4 alpha subunits (Kv4.2, Kv4.3) to enhance channel surface expression, accelerate recovery from inactivation, and modulate voltage dependence. In the heart, KCNIP2 is essential for the transient outward potassium current (Ito), which shapes the cardiac action potential. In the brain, it regulates dendritic excitability and synaptic plasticity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNIP2 Knockout HEK293 Cell Line | EDJ-KQ9181 | Human | 30819 | Details Get a Quote |
| KCNIP2 Knockout HCT 116 Cell Line | EDJ-KQ35730 | Human | 30819 | Details Get a Quote |
| KCNIP2 Knockout HeLa Cell Line | EDJ-KQ56152 | Human | 30819 | Details Get a Quote |
| KCNIP2 Knockout A-549 Cell Line | EDJ-KQ64642 | Human | 30819 | Details Get a Quote |
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