KCNJ9
Potassium Inwardly Rectifying Channel Subfamily J Member 9
Gene Information Card
| Symbol | KCNJ9 |
|---|---|
| Full Name | Potassium Inwardly Rectifying Channel Subfamily J Member 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.2 |
| NCBI Gene ID | 3765 ncbi.nlm.nih.gov/gene/3765 |
| Ensembl ID | ENSG00000171385 |
| UniProt ID | Q92806 |
| OMIM ID | 600932 |
| HGNC ID | 6268 |
| Aliases | GIRK3, KIR3.3 |
Description
KCNJ9 (Potassium Inwardly Rectifying Channel Subfamily J Member 9) encodes the GIRK3 (Kir3.3) protein, a member of the G protein-coupled inwardly rectifying potassium (GIRK) channel family. These channels are activated by pertussis toxin-sensitive G proteins and play critical roles in regulating neuronal excitability, heart rate, and hormone secretion. GIRK3 forms functional heterotetramers with other GIRK subunits (e.g., GIRK1, GIRK2) and is widely expressed in the brain, heart, and endocrine tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brugada Syndrome | Potential modulation of cardiac action potential via altered potassium conductance; loss-of-function variants may predispose to arrhythmia | ClinVar |
| Epilepsy | Altered neuronal excitability due to disrupted GIRK channel function; rare variants implicated in seizure disorders | NCBI Gene |
| Addiction (substance use disorder) | GIRK3 modulates dopamine and opioid signaling; polymorphisms associated with alcohol and cocaine dependence | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Heart (left ventricle) | 8.3 | Low |
| Pancreas | 6.1 | Low |
| Adrenal gland | 4.7 | Low |
| Testis | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous |
| H9c2 (cardiomyoblast) | 5.8 | Cardiac model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Reduced channel conductance; associated with arrhythmia risk |
| c.457G>A (p.Glu153Lys) | Missense | <0.01% | Altered G protein sensitivity; potential gain-of-function |
| c.784_786del (p.Lys262del) | In-frame deletion | <0.01% | Loss of surface expression; linked to epilepsy |
Mutation functional classification
Loss of Function (LOF)
p.Thr34Met and p.Lys262del reduce or abolish potassium conductance, leading to hyperexcitability.
Gain of Function (GOF)
p.Glu153Lys may enhance channel activity, potentially causing bradycardia or neuronal silencing.
Dominant Negative (DN)
Not well documented; heterotetrameric assembly may allow dominant-negative effects in some variants.
View complete mutation data：
Gene Ontology (GO)
Pathways
• G protein signaling (KEGG:04080)
• Cholinergic synapse (KEGG:04725)
• Dopaminergic synapse (KEGG:04728)
Protein Summary
The GIRK3 protein (UniProt Q92806) is a 393-amino acid integral membrane protein with two transmembrane domains and a pore-forming loop. It assembles into functional tetramers that conduct potassium ions into cells upon activation by Gβγ subunits released from Gi/o proteins. GIRK3 is predominantly expressed in neurons, where it mediates slow inhibitory postsynaptic potentials, and in cardiac myocytes, contributing to heart rate regulation. Its C-terminal domain contains trafficking signals that regulate surface expression and endocytosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ9 Knockout HEK293 Cell Line | EDJ-KQ5040 | Human | 3765 | Details Get a Quote |
| KCNJ9 Knockout HeLa Cell Line | EDJ-KQ53716 | Human | 3765 | Details Get a Quote |
| KCNJ9 Knockout A-549 Cell Line | EDJ-KQ62191 | Human | 3765 | Details Get a Quote |
| KCNJ9 Knockout HCT 116 Cell Line | EDJ-KQ70679 | Human | 3765 | Details Get a Quote |
