KCNJ5
Potassium Inwardly Rectifying Channel Subfamily J Member 5
Gene Information Card
| Symbol | KCNJ5 |
|---|---|
| Full Name | Potassium Inwardly Rectifying Channel Subfamily J Member 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q24.3 |
| NCBI Gene ID | 3762 ncbi.nlm.nih.gov/gene/3762 |
| Ensembl ID | ENSG00000120457 |
| UniProt ID | P48544 |
| OMIM ID | 600734 |
| HGNC ID | 6266 |
| Aliases | GIRK4, KATP1, CIR, KCNJ5-AS1 |
Description
KCNJ5 encodes the G protein-activated inward rectifier potassium channel 4 (GIRK4), a subunit of heterotetrameric channels that regulate resting membrane potential and electrical excitability. It is highly expressed in the adrenal cortex and heart, where it modulates aldosterone secretion and cardiac pacemaker activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aldosterone-producing adenoma (APA) | Somatic gain-of-function mutations (e.g., G151R, L168R) cause constitutive channel activity, leading to membrane depolarization, increased aldosterone synthase expression, and autonomous aldosterone secretion. | ClinVar, OMIM |
| Long QT syndrome 13 (LQT13) | Loss-of-function mutations reduce potassium conductance, prolonging cardiac repolarization and increasing arrhythmia risk. | ClinVar, OMIM |
| Hypertension with hypokalemia | Germline gain-of-function mutations cause early-onset hypertension, hypokalemia, and bilateral adrenal hyperplasia. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 32.5 | High |
| Heart | 18.2 | Medium |
| Brain | 12.1 | Medium |
| Kidney | 5.3 | Low |
| Liver | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| H295R (adrenocortical) | 45.0 | High expression |
| HEK293 | 8.5 | Moderate |
| K562 | 2.1 | Low |
| SH-SY5Y | 6.7 | Moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G151R | Missense | ~40% of APA cases | Gain-of-function; constitutive channel opening |
| L168R | Missense | ~20% of APA cases | Gain-of-function; altered ion selectivity |
| T158A | Missense | Rare | Gain-of-function; increased current density |
| G387R | Missense | Rare | Loss-of-function; associated with LQT13 |
Mutation functional classification
Loss of Function (LOF)
Reduced potassium conductance, prolonged cardiac repolarization (e.g., G387R).
Gain of Function (GOF)
Constitutive channel activity, membrane depolarization, aldosterone excess (e.g., G151R, L168R).
Dominant Negative (DN)
Not reported for KCNJ5.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled inward rectifier potassium channel activity | • potassium ion transmembrane transport |
| • regulation of membrane potential | • cellular response to hormone stimulus |
Pathways
• G protein-activated inward rectifier potassium channel signaling
• Aldosterone synthesis and secretion
Protein Summary
GIRK4 is a 419-amino acid protein with two transmembrane domains and a pore-forming loop. It forms functional channels as a heterotetramer with GIRK1 (KCNJ3). Channel opening is triggered by Gβγ subunits released from activated G protein-coupled receptors. In the adrenal zona glomerulosa, GIRK4 maintains the hyperpolarized resting potential necessary for angiotensin II and potassium sensing.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ5 Knockout HEK293 Cell Line | EDJ-KQ5065 | Human | 3762 | Details Get a Quote |
| KCNJ5 Knockout HeLa Cell Line | EDJ-KQ53714 | Human | 3762 | Details Get a Quote |
| KCNJ5 Knockout A-549 Cell Line | EDJ-KQ62190 | Human | 3762 | Details Get a Quote |
| KCNJ5 Knockout HCT 116 Cell Line | EDJ-KQ70677 | Human | 3762 | Details Get a Quote |
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