KCNJ4
Potassium Inwardly Rectifying Channel Subfamily J Member 4
Gene Information Card
| Symbol | KCNJ4 |
|---|---|
| Full Name | Potassium Inwardly Rectifying Channel Subfamily J Member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 3761 ncbi.nlm.nih.gov/gene/3761 |
| Ensembl ID | ENSG00000168135 |
| UniProt ID | P48050 |
| OMIM ID | 600504 |
| HGNC ID | 6266 |
| Aliases | IRK3, Kir2.3, HIRK2, KIR2.3 |
Description
KCNJ4 encodes the Kir2.3 (IRK3) protein, a member of the inwardly rectifying potassium channel family. These channels are critical for maintaining resting membrane potential and regulating neuronal and cardiac excitability. Kir2.3 is predominantly expressed in the brain and heart, where it mediates potassium ion flux in response to physiological stimuli.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Andersen-Tawil Syndrome (ATS) | Loss-of-function mutations in KCNJ4 reduce inward rectifier current, leading to cardiac arrhythmias and periodic paralysis. | ClinVar, OMIM |
| Long QT Syndrome | Altered Kir2.3 function can prolong cardiac repolarization, increasing arrhythmia risk. | ClinVar |
| Epilepsy | KCNJ4 variants may disrupt neuronal potassium homeostasis, contributing to seizure susceptibility. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Heart (left ventricle) | 8.3 | Low |
| Skeletal muscle | 3.1 | Low |
| Kidney | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.0 | Neuronal model |
| HEK293 (embryonic kidney) | 2.5 | Low endogenous expression |
| H9c2 (cardiomyoblast) | 7.8 | Cardiac model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.652C>T (p.Arg218Cys) | Missense | <0.01% | Reduced channel conductance (loss-of-function) |
| c.901G>A (p.Gly301Arg) | Missense | <0.01% | Impaired membrane trafficking |
| c.1124T>C (p.Leu375Pro) | Missense | <0.01% | Dominant-negative effect on channel assembly |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg218Cys reduce potassium conductance, leading to Andersen-Tawil syndrome phenotypes.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in KCNJ4.
Dominant Negative (DN)
p.Leu375Pro disrupts tetrameric channel assembly, reducing overall current.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACT:388396 – Inwardly rectifying potassium channels
• KEGG:hsa04270 – Vascular smooth muscle contraction
• KEGG:hsa05414 – Dilated cardiomyopathy
Protein Summary
Kir2.3 is a 445-amino acid transmembrane protein that forms homotetrameric or heterotetrameric channels. It contains two transmembrane domains (M1 and M2) and a pore-forming loop (H5). The channel conducts potassium ions into cells more readily than outward, contributing to membrane hyperpolarization. Kir2.3 is regulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and pH, and is essential for normal neuronal and cardiac excitability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ4 Knockout HEK293 Cell Line | EDJ-KQ5034 | Human | 3761 | Details Get a Quote |
| KCNJ4 Knockout HeLa Cell Line | EDJ-KQ53713 | Human | 3761 | Details Get a Quote |
| KCNJ4 Knockout A-549 Cell Line | EDJ-KQ62189 | Human | 3761 | Details Get a Quote |
| KCNJ4 Knockout HCT 116 Cell Line | EDJ-KQ70676 | Human | 3761 | Details Get a Quote |
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