KCNJ6
Potassium Inwardly Rectifying Channel Subfamily J Member 6
Gene Information Card
| Symbol | KCNJ6 |
|---|---|
| Full Name | Potassium Inwardly Rectifying Channel Subfamily J Member 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.13 |
| NCBI Gene ID | 3763 ncbi.nlm.nih.gov/gene/3763 |
| Ensembl ID | ENSG00000157542 |
| UniProt ID | P48051 |
| OMIM ID | 600877 |
| HGNC ID | 6267 |
| Aliases | GIRK2, KATP2, Kir3.2, BIR1, hiGIRK2 |
Description
The KCNJ6 gene encodes the G protein-activated inwardly rectifying potassium channel 2 (GIRK2), a member of the Kir3 subfamily. GIRK2 forms homomeric or heteromeric channels that mediate postsynaptic inhibitory neurotransmission and regulate neuronal excitability. The channel is activated by G protein beta-gamma subunits and modulated by intracellular ATP, PIP2, and ethanol. Mutations in KCNJ6 are associated with neurodevelopmental disorders, including Weaver syndrome and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Weaver syndrome | Gain-of-function mutations in KCNJ6 lead to constitutive activation of GIRK2 channels, causing hyperpolarization and impaired neuronal development. | ClinVar, OMIM |
| Autism spectrum disorder | Missense variants in KCNJ6 alter channel gating and synaptic signaling, contributing to ASD pathophysiology. | ClinVar, PubMed |
| Episodic ataxia type 1 (EA1) | Rare KCNJ6 variants may disrupt cerebellar Purkinje cell firing, leading to motor incoordination. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebellum | 15.2 | High |
| Cerebral cortex | 10.8 | High |
| Heart | 0.5 | Low |
| Pancreas | 0.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 8.7 | Neuronal cell line |
| HEK293 | 0.2 | Low endogenous expression |
| SK-N-SH | 9.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.512G>A (p.Gly171Asp) | Missense | 0.001% | Gain-of-function; causes Weaver syndrome |
| c.785C>T (p.Thr262Ile) | Missense | 0.0005% | Altered channel kinetics; associated with ASD |
| c.1018G>A (p.Gly340Ser) | Missense | 0.0002% | Reduced G protein activation; loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair channel opening or reduce surface expression, e.g., p.Gly340Ser, lead to decreased potassium conductance and neuronal hyperexcitability.
Gain of Function (GOF)
Mutations such as p.Gly171Asp cause constitutive channel opening, resulting in persistent hyperpolarization and disrupted neuronal development.
Dominant Negative (DN)
Heterozygous mutations that produce non-functional subunits can oligomerize with wild-type subunits, reducing overall channel activity.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway | • potassium ion transmembrane transport |
| • inward rectifier potassium channel activity | • G protein beta-subunit binding |
| • plasma membrane | • synapse |
Pathways
• G protein signaling (Kir3 channels)
• Dopamine-DARPP32 feedback in cAMP signaling
• Opioid signaling
Protein Summary
GIRK2 (Kir3.2) is a 423-amino acid integral membrane protein with two transmembrane domains (M1 and M2) and a pore-forming loop. It assembles as a tetramer to form a potassium-selective channel that conducts inward rectifying currents. The channel is activated by G protein beta-gamma subunits released upon GPCR activation, and is modulated by intracellular ATP, PIP2, and ethanol. GIRK2 is highly expressed in brain regions including cerebellum, hippocampus, and cortex, where it mediates slow inhibitory postsynaptic potentials. Pathogenic mutations alter channel gating, leading to neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ6 Knockout HEK293 Cell Line | EDJ-KQ5035 | Human | 3763 | Details Get a Quote |
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