KCNJ11
Potassium Inwardly Rectifying Channel Subfamily J Member 11
Gene Information Card
| Symbol | KCNJ11 |
|---|---|
| Full Name | Potassium Inwardly Rectifying Channel Subfamily J Member 11 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 3767 ncbi.nlm.nih.gov/gene/3767 |
| Ensembl ID | ENSG00000187486 |
| UniProt ID | Q14654 |
| OMIM ID | 600937 |
| HGNC ID | 6257 |
| Aliases | Kir6.2, BIR, HHF2, PHHI, TNDM3, IKATP |
Description
The KCNJ11 gene encodes the Kir6.2 protein, a pore-forming subunit of the ATP-sensitive potassium (K_ATP) channel. This channel couples cellular metabolism to electrical activity by regulating potassium ion flux across the plasma membrane. In pancreatic beta-cells, K_ATP channels control insulin secretion; in neurons and muscle, they modulate excitability. Loss-of-function mutations cause congenital hyperinsulinism, while gain-of-function mutations lead to neonatal diabetes mellitus and DEND syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Permanent Neonatal Diabetes Mellitus (PNDM) | Gain-of-function mutations reduce K_ATP channel closure, impairing insulin secretion | ClinVar, OMIM |
| Transient Neonatal Diabetes Mellitus (TNDM) | Gain-of-function mutations cause temporary hyperglycemia in infancy | OMIM |
| DEND Syndrome | Severe gain-of-function mutations cause developmental delay, epilepsy, and neonatal diabetes | OMIM |
| Congenital Hyperinsulinism (HHF2) | Loss-of-function mutations keep K_ATP channels closed, causing unregulated insulin release | ClinVar, OMIM |
| Maturity-Onset Diabetes of the Young (MODY) | Rare KCNJ11 variants may contribute to monogenic diabetes | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 31.2 | High |
| Brain | 12.5 | Medium |
| Heart | 8.9 | Medium |
| Skeletal Muscle | 6.3 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (beta-cell) | 45.0 | High expression |
| SH-SY5Y (neuronal) | 18.0 | Moderate expression |
| HeLa | 2.5 | Low expression |
| HEK293 | 1.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.R201H | Missense | ~30% of PNDM cases | Gain-of-function; reduces ATP sensitivity |
| p.V59M | Missense | ~10% of DEND syndrome | Gain-of-function; severe channel opening |
| p.E23K | Missense | Common polymorphism (up to 40% in some populations) | Modest gain-of-function; associated with type 2 diabetes risk |
| p.F55L | Missense | Rare | Loss-of-function; causes hyperinsulinism |
| p.G334D | Missense | Rare | Loss-of-function; impairs channel trafficking |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce channel activity (e.g., p.F55L, p.G334D) cause congenital hyperinsulinism by keeping K_ATP channels closed, leading to persistent insulin secretion.
Gain of Function (GOF)
Mutations that increase channel activity (e.g., p.R201H, p.V59M) cause neonatal diabetes by preventing K_ATP channel closure, inhibiting insulin release.
Dominant Negative (DN)
Some KCNJ11 mutations (e.g., p.G334D) can exert dominant-negative effects by co-assembling with wild-type subunits, impairing channel function in heterozygous individuals.
View complete mutation data：
Gene Ontology (GO)
Pathways
• K_ATP channel complex (Reactome: R-HSA-1296025)
• Regulation of insulin secretion (Reactome: R-HSA-422356)
• Glucose homeostasis (KEGG: hsa04910)
• Type II diabetes mellitus (KEGG: hsa04930)
Protein Summary
Kir6.2 (KCNJ11) is a 390-amino acid integral membrane protein with two transmembrane domains (M1 and M2) and a pore-forming loop. It assembles as a heterooctamer with four sulfonylurea receptor (SUR1 or SUR2) subunits to form functional K_ATP channels. The channel is inhibited by intracellular ATP and activated by MgADP, linking metabolic state to membrane excitability. Mutations in Kir6.2 alter ATP sensitivity, leading to dysregulated insulin secretion and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNJ11 Knockout HEK293 Cell Line | EDJ-KQ3740 | Human | 3767 | Details Get a Quote |
| KCNJ11 Knockout HCT 116 Cell Line | EDJ-KQ25799 | Human | 3767 | Details Get a Quote |
| KCNJ11 Knockout HeLa Cell Line | EDJ-KQ53718 | Human | 3767 | Details Get a Quote |
| KCNJ11 Knockout A-549 Cell Line | EDJ-KQ62193 | Human | 3767 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
