KCNJ8
Potassium Inwardly Rectifying Channel Subfamily J Member 8
Gene Information Card
| Symbol | KCNJ8 |
|---|---|
| Full Name | Potassium Inwardly Rectifying Channel Subfamily J Member 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p12.1 |
| NCBI Gene ID | 3764 ncbi.nlm.nih.gov/gene/3764 |
| Ensembl ID | ENSG00000162728 |
| UniProt ID | Q15842 |
| OMIM ID | 600935 |
| HGNC ID | 6269 |
| Aliases | Kir6.1, uKATP-1, KATP1 |
Description
KCNJ8 encodes the Kir6.1 subunit of ATP-sensitive potassium (K_ATP) channels. These channels couple cellular metabolism to membrane excitability by opening when intracellular ATP levels are low. Kir6.1 is widely expressed in vascular smooth muscle, cardiac myocytes, and pancreatic beta-cells, regulating vascular tone, cardiac protection, and insulin secretion. Gain-of-function mutations cause Cantú syndrome, characterized by hypertrichosis, cardiomegaly, and skeletal abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cantú syndrome | Gain-of-function mutations in KCNJ8 increase K_ATP channel activity, leading to persistent vasodilation, hypertrichosis, and cardiac hypertrophy. | OMIM #239850; ClinVar |
| Early repolarization syndrome | Missense variants (e.g., S422L) enhance channel current, predisposing to ventricular fibrillation. | PMID 22985903; ClinVar |
| Coronary artery spasm | KCNJ8 variants may alter vascular smooth muscle excitability, contributing to vasospasm. | PMID 22985903 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 8.3 | Low |
| Smooth muscle | 15.1 | Medium |
| Pancreas | 6.7 | Low |
| Brain | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC | 18.4 | Endothelial cells |
| Aortic smooth muscle cells | 22.1 | Vascular smooth muscle |
| Cardiomyocytes (iPS-derived) | 14.7 | Cardiac muscle cells |
| HEK293 | 2.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1265C>T (p.Ser422Leu) | Missense | Rare | Gain-of-function; associated with early repolarization syndrome |
| c.1018G>A (p.Gly340Arg) | Missense | Rare | Gain-of-function; linked to Cantú syndrome |
| c.1129G>A (p.Glu377Lys) | Missense | Rare | Gain-of-function; Cantú syndrome |
Mutation functional classification
Loss of Function (LOF)
Not reported in KCNJ8; loss-of-function mutations in KCNJ11 cause congenital hyperinsulinism.
Gain of Function (GOF)
Common mechanism in Cantú syndrome and early repolarization syndrome; increased K_ATP current.
Dominant Negative (DN)
Not described for KCNJ8.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ATP-sensitive potassium channels (Reactome R-HSA-1296067)
• Cardiac conduction (KEGG hsa05414)
• Insulin secretion (KEGG hsa04911)
Protein Summary
Kir6.1 is a 424-amino acid protein with two transmembrane domains (M1 and M2) and a pore-forming loop. It assembles as a tetramer with sulfonylurea receptor (SUR2B) to form functional K_ATP channels. The channel is inhibited by intracellular ATP and activated by MgADP, linking metabolic state to membrane potential. Kir6.1 is critical for coronary vasodilation and cardiac ischemic preconditioning.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ8 Knockout HEK293 Cell Line | EDJ-KQ1856 | Human | 3764 | Details Get a Quote |
| KCNJ8 Knockout A-549 Cell Line | EDJ-KQ21721 | Human | 3764 | Details Get a Quote |
| KCNJ8 Knockout HeLa Cell Line | EDJ-KQ53715 | Human | 3764 | Details Get a Quote |
| KCNJ8 Knockout HCT 116 Cell Line | EDJ-KQ70678 | Human | 3764 | Details Get a Quote |
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