KCNJ2 (Kir2.1) Potassium Channel Gene
Genetic insights into Andersen-Tawil syndrome, atrial fibrillation, and periodic paralysis
Gene Information Card
| Symbol | KCNJ2 |
|---|---|
| Full Name | Potassium voltage-gated channel subfamily J member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q24.3 |
| NCBI Gene ID | 3759 ncbi.nlm.nih.gov/gene/3759 |
| Ensembl ID | ENSG00000171314 |
| UniProt ID | P63252 |
| OMIM ID | 600681 |
| HGNC ID | 6263 |
| Aliases | IRK1, ATFB9, HHF2, LQT7, SQT3, KIR2.1 |
Description
The KCNJ2 gene encodes the inward rectifier potassium channel Kir2.1, which is critical for maintaining the resting membrane potential and regulating excitability in cardiac and skeletal muscle. Mutations in KCNJ2 are associated with Andersen-Tawil syndrome, a form of long QT syndrome (LQT7), short QT syndrome (SQT3), and familial atrial fibrillation. The channel contributes to the cardiac IK1 current, essential for the terminal repolarization phase and resting potential stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Andersen-Tawil syndrome (ATS1) | Loss-of-function mutations reduce IK1 current, leading to prolonged action potential and arrhythmias; also affects skeletal muscle and developmental features. | ClinVar, OMIM |
| Long QT syndrome 7 (LQT7) | Dominant-negative mutations reduce channel function, prolonging cardiac repolarization and increasing risk of ventricular arrhythmias. | ClinVar, OMIM |
| Short QT syndrome 3 (SQT3) | Gain-of-function mutations increase IK1, shortening action potential duration and predisposing to atrial and ventricular fibrillation. | ClinVar, OMIM |
| Familial atrial fibrillation (ATFB9) | Gain-of-function mutations enhance IK1, leading to shortened atrial refractory period and arrhythmia susceptibility. | ClinVar, OMIM |
| Periodic paralysis (hypokalemic) | Mutations alter channel function, affecting skeletal muscle excitability and causing episodic weakness. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 23.5 | High expression in cardiac muscle, particularly ventricles and atria. |
| Skeletal muscle | 18.2 | Moderate expression in skeletal muscle. |
| Brain | 5.1 | Low expression in various brain regions. |
| Liver | 1.2 | Very low expression. |
| Kidney | 0.8 | Minimal expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 25.0 | High expression, functional IK1 current. |
| Skeletal muscle myotubes | 15.0 | Moderate expression. |
| HEK293 | 0.5 | Low endogenous expression; used for heterologous expression studies. |
| HeLa | 0.2 | Very low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R67W | Missense | Rare | Dominant-negative loss-of-function; associated with Andersen-Tawil syndrome. |
| D71V | Missense | Rare | Dominant-negative loss-of-function; causes ATS1. |
| T75R | Missense | Rare | Gain-of-function; linked to short QT syndrome. |
| V93I | Missense | Polymorphism | Benign variant; no known disease association. |
| G144A | Missense | Rare | Loss-of-function; associated with ATS1. |
| R218W | Missense | Rare | Dominant-negative; causes LQT7. |
Mutation functional classification
Loss of Function (LOF)
Reduced or absent Kir2.1 channel activity, leading to decreased IK1 current, prolonged action potential, and increased arrhythmia risk (e.g., Andersen-Tawil syndrome).
Gain of Function (GOF)
Increased Kir2.1 channel activity, enhancing IK1 current, shortening action potential duration, and predisposing to atrial fibrillation or short QT syndrome.
Dominant Negative (DN)
Mutant subunits co-assemble with wild-type subunits, impairing channel function in a dominant manner, often seen in ATS1 and LQT7.
View complete mutation data：
Gene Ontology (GO)
| • Inward rectifier potassium channel activity | • Voltage-gated potassium channel activity |
| • Potassium ion transmembrane transport | • Regulation of membrane potential |
| • Cardiac muscle cell action potential | • Skeletal muscle contraction |
Pathways
• Cardiac muscle contraction
• Potassium channels
• Ion transport
• Action potential regulation
Protein Summary
Kir2.1 is a 427-amino acid protein with two transmembrane domains (M1 and M2) and a pore-forming loop. It assembles as a tetramer to form a functional inward rectifier potassium channel. The channel conducts potassium ions into the cell more readily than outward, helping to stabilize the resting membrane potential near the potassium equilibrium potential. In the heart, Kir2.1 contributes to the IK1 current, which is crucial for the terminal repolarization phase and maintenance of resting potential. Mutations can disrupt channel function, leading to various cardiac and skeletal muscle disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ2 Knockout HEK293 Cell Line | EDJ-KQ5032 | Human | 3759 | Details Get a Quote |
| KCNJ2 Knockout HeLa Cell Line | EDJ-KQ53711 | Human | 3759 | Details Get a Quote |
| KCNJ2 Knockout A-549 Cell Line | EDJ-KQ62187 | Human | 3759 | Details Get a Quote |
| KCNJ2 Knockout HCT 116 Cell Line | EDJ-KQ70674 | Human | 3759 | Details Get a Quote |
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