KCNIP3 (Potassium Voltage-Gated Channel Interacting Protein 3)
A calcium-binding protein that modulates A-type potassium channels and functions as a transcriptional repressor.
Gene Information Card
| Symbol | KCNIP3 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Interacting Protein 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q21.1 |
| NCBI Gene ID | 30818 ncbi.nlm.nih.gov/gene/30818 |
| Ensembl ID | ENSG00000115041 |
| UniProt ID | Q9Y2W7 |
| OMIM ID | 604662 |
| HGNC ID | 15521 |
| Aliases | CSEN, DREAM, KCHIP3 |
Description
KCNIP3 (potassium voltage-gated channel interacting protein 3) encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins. The encoded protein is a calcium-binding protein that modulates the gating properties of Kv4 channels, thereby regulating A-type potassium currents. Additionally, KCNIP3 functions as a transcriptional repressor (DREAM) by binding to DNA response elements in a calcium-dependent manner. It is implicated in neuronal excitability, pain modulation, and cardiac function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | KCNIP3 interacts with presenilin and modulates gamma-secretase activity, potentially affecting amyloid-beta production. | PMID: 10624965 |
| Cardiac arrhythmia | Altered KCNIP3 expression or function can disrupt Kv4 channel-mediated cardiac repolarization, contributing to arrhythmogenesis. | PMID: 15642749 |
| Pain perception | As DREAM, KCNIP3 represses prodynorphin expression; loss of repression may alter pain sensitivity. | PMID: 11804586 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.2 | High |
| Heart | 12.5 | Medium |
| Skeletal muscle | 6.8 | Low |
| Pancreas | 4.1 | Low |
| Liver | 1.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | Neuronal model |
| HEK 293 (embryonic kidney) | 2.5 | Low endogenous expression |
| K562 (leukemia) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.374G>A (p.Arg125His) | Missense | <0.01% | Altered calcium binding and transcriptional repression activity |
| c.512C>T (p.Pro171Leu) | Missense | <0.01% | Reduced Kv4 channel modulation |
Mutation functional classification
Loss of Function (LOF)
p.Arg125His reduces calcium-dependent DNA binding, impairing transcriptional repression.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
p.Pro171Leu may interfere with wild-type KCNIP3 function in Kv4 channel complexes.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated potassium channel activity | • calcium ion binding |
| • transcription cis-regulatory region binding | • protein homodimerization activity |
| • regulation of membrane repolarization |
Pathways
• Kv4-mediated A-type potassium current
• Calcium signaling
• Notch signaling (via presenilin interaction)
Protein Summary
KCNIP3 (calsenilin/DREAM) is a 256-amino-acid protein containing four EF-hand calcium-binding domains. It forms tetramers that associate with Kv4 potassium channels to accelerate inactivation and modulate channel density. In the nucleus, it binds to DRE (downstream regulatory element) sites to repress transcription of target genes such as prodynorphin. Its dual role in ion channel regulation and gene expression links it to neurological and cardiac disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNIP3 Knockout HEK293 Cell Line | EDJ-KQ8411 | Human | 30818 | Details Get a Quote |
| KCNIP3 Knockout HCT 116 Cell Line | EDJ-KQ35729 | Human | 30818 | Details Get a Quote |
| KCNIP3 Knockout HeLa Cell Line | EDJ-KQ56151 | Human | 30818 | Details Get a Quote |
| KCNIP3 Knockout A-549 Cell Line | EDJ-KQ64641 | Human | 30818 | Details Get a Quote |
