KCNJ3 (GIRK1): Inwardly Rectifying Potassium Channel Subunit
A key regulator of neuronal excitability and cardiac pacemaker activity, implicated in epilepsy, cardiac arrhythmias, and cancer.
Gene Information Card
| Symbol | KCNJ3 |
|---|---|
| Full Name | Potassium voltage-gated channel subfamily J member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q24.1 |
| NCBI Gene ID | 3760 ncbi.nlm.nih.gov/gene/3760 |
| Ensembl ID | ENSG00000144355 |
| UniProt ID | P48549 |
| OMIM ID | 601534 |
| HGNC ID | 6266 |
| Aliases | GIRK1, KGA, KIR3.1, BIR1 |
Description
KCNJ3 encodes the G protein-activated inward rectifier potassium channel 1 (GIRK1), a subunit that assembles with other GIRK subunits (e.g., GIRK2, GIRK3, GIRK4) to form functional channels. These channels mediate inhibitory neurotransmission in the brain and regulate heart rate in response to G protein-coupled receptor activation. KCNJ3 is widely expressed, with highest levels in the brain and heart. Mutations and dysregulation of KCNJ3 have been linked to epilepsy, cardiac arrhythmias, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy | Loss-of-function mutations reduce GIRK1-mediated potassium conductance, leading to neuronal hyperexcitability. | ClinVar, OMIM |
| Long QT syndrome (rare) | Gain-of-function mutations may prolong cardiac repolarization, increasing arrhythmia risk. | ClinVar, OMIM |
| Atrial fibrillation | Altered GIRK1 expression/function contributes to abnormal atrial electrical activity. | NCBI, PubMed |
| Cancer (e.g., breast, lung) | Aberrant KCNJ3 expression modulates cell proliferation and migration; oncogenic or tumor-suppressive roles depending on context. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum, cortex) | High (e.g., 20-30 nTPM) | High |
| Heart (atrial appendage) | Moderate (e.g., 10-15 nTPM) | Moderate |
| Liver | Low (e.g., 2-5 nTPM) | Low |
| Kidney | Low (e.g., 1-3 nTPM) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High (e.g., 25 nTPM) | Neuronal model |
| MCF7 (breast cancer) | Moderate (e.g., 12 nTPM) | Hormone-responsive |
| A549 (lung cancer) | Low (e.g., 3 nTPM) | Epithelial-like |
| HepG2 (liver cancer) | Low (e.g., 2 nTPM) | Hepatic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.679C>T (p.Arg227Cys) | Missense | Rare (<0.01%) | Loss-of-function; associated with epilepsy |
| c.1018G>A (p.Gly340Ser) | Missense | Rare (<0.01%) | Gain-of-function; linked to long QT syndrome |
| c.1120A>G (p.Ile374Val) | Missense | Rare (<0.01%) | Uncertain significance; possibly benign |
| c.1234C>T (p.Arg412*) | Nonsense | Very rare | Loss-of-function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Reduced potassium conductance leads to neuronal hyperexcitability (epilepsy) and impaired cardiac repolarization.
Gain of Function (GOF)
Increased potassium conductance can shorten or prolong action potentials, contributing to arrhythmias.
Dominant Negative (DN)
Mutant subunits may co-assemble with wild-type subunits, reducing overall channel function.
View complete mutation data：
Gene Ontology (GO)
| • G protein-activated inward rectifier potassium channel activity | • Potassium ion transmembrane transport |
| • Plasma membrane | • Response to G protein-coupled receptor signaling |
Pathways
• G protein-activated inward rectifier potassium channel (GIRK) signaling
• GPCR downstream signaling
• Cardiac conduction
• Neurotransmitter release
Protein Summary
The KCNJ3 protein (GIRK1) is a 501-amino acid integral membrane protein with two transmembrane domains and a pore-forming loop. It forms functional channels as homo- or heterotetramers with other GIRK subunits. GIRK1 is activated by G protein beta-gamma subunits released upon GPCR stimulation, mediating potassium efflux that hyperpolarizes the cell membrane. This underlies its role in inhibitory neurotransmission and cardiac pacemaking. Post-translational modifications include phosphorylation and palmitoylation, which regulate channel trafficking and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ3 Knockout HEK293 Cell Line | EDJ-KQ5039 | Human | 3760 | Details Get a Quote |
| KCNJ3 Knockout HeLa Cell Line | EDJ-KQ53712 | Human | 3760 | Details Get a Quote |
| KCNJ3 Knockout A-549 Cell Line | EDJ-KQ62188 | Human | 3760 | Details Get a Quote |
| KCNJ3 Knockout HCT 116 Cell Line | EDJ-KQ70675 | Human | 3760 | Details Get a Quote |
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