KCNJ11

Official Full Name

potassium inwardly rectifying channel subfamily J member 11

Organism

Homo sapiens

Gene ID

3767

Background

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

Synonyms

BIR; HHF2; PHHI; IKATP; PNDM2; TNDM3; KIR6.2; MODY13

Cat.No.	Product Name	Price
CSC-DC007962	Panoply™ Human KCNJ11 Knockdown Stable Cell Line	Inquiry
CSC-SC007962	Panoply™ Human KCNJ11 Over-expressing Stable Cell Line	Inquiry
CSC-RT2053	KCNJ11 Knockout Cell Line-HeLa	Inquiry
CLKO-1914	KCNJ11 KO Cell Lysate-HeLa	Inquiry

Cat.No.	Product Name	Price
AD08418Z	Human KCNJ11 adenoviral particles	Inquiry
LV15984L	human KCNJ11 (NM_000525) lentivirus particles	Inquiry
LV15985L	human KCNJ11 (NM_001166290) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH323203	shRNA set against Human KCNJ11 (NM_000525.3)	Inquiry
SHH323207	shRNA set against Mouse KCNJ11 (NM_010602.3)	Inquiry
SHL189714	shRNA set against Rat Kcnj11(NM_031358.3)	Inquiry
SHL189750	shRNA set against Human KCNJ11(NM_000525.3)	Inquiry
SHW009552	shRNA set against Danio rerio KCNJ11 (NM_001039827)	Inquiry

Cat.No.	Product Name	Price
CDCL123057	Human KCNJ11 ORF clone (NM_001166290.1)	Inquiry
CDCR336760	Human KCNJ11 ORF Clone(NM_000525.3)	Inquiry
CDCR379696	Rat Kcnj11 ORF Clone(NM_031358.3)	Inquiry
CDFH009643	Human KCNJ11 cDNA Clone(NM_000525.3)	Inquiry
CDFH009644	Human KCNJ11 cDNA Clone(NM_001166290.1)	Inquiry
CDFR012663	Rat Kcnj11 cDNA Clone(NM_031358.3)	Inquiry
MiUTR1H-05134	KCNJ11 miRNA 3'UTR clone	Inquiry
MiUTR1R-02818	KCNJ11 miRNA 3'UTR clone	Inquiry
MiUTR3H-03754	KCNJ11 miRNA 3'UTR clone	Inquiry
CDCB171027	Danio rerio KCNJ11 ORF Clone (NM_001039827)	Inquiry
CDCB181010	Rabbit KCNJ11 ORF clone (NM_001082017.1)	Inquiry
CDCL151210	Mouse Kcnj11 ORF clone (NM_001204411.1)	Inquiry
CDCR249297	Mouse Kcnj11 ORF Clone(NM_010602.3)	Inquiry
CDCS405721	Human KCNJ11 ORF Clone (BC112358)	Inquiry

Detailed Information

Recent Research

The KCNJ11 gene, a member of the potassium channel gene family, is located at 11p15.1 and has no intron. This gene encodes an inward rectifying potassium ion channel (Kir6.2). Kir6.2 protein forms KATP channel together with high affinity sulfonylurea receptor 1 (SUR1). SUR1 is encoded by ABCC8 gene next to KCNJ11 gene. The Kir6.2 protein is a 390-amino acid protein with two transmembrane domains (M1 and M2) and intracellular N-and C-terminals. Structurally, Kir6.2 tetramer forms a hole, which is located in the KATP channel hole of the pancreatic cytoplasmic membrane and surrounded by 4 high-affinity SUR1 subunits. This channel modulates insulin production and secretion through glucose metabolism.

Kir6.2 and insulin secretion

The Kir6.2 protein, coupled with the SUR1 protein in the KATP channel, mediates insulin secretion. This pathway involves a wide range of physiological responses. The increase in glucose causes potassium to enter the cell through the KATP channel. ADP is converted into ATP in the presence of magnesium (Mg). The ATP then closes the KATP channel by binding to Kir6.2, increasing the intracellular potassium ion concentration, which depolarizes the cell membrane and subsequently activates calcium ion (Ca²⁺) channel. Ca²⁺ is a ubiquitous intracellular second messenger that is critical for cellular functioning. These calcium channels affect voltage dependent potassium channels to repolarize the cell membrane, leading to closure of the voltage-dependent calcium channels. Increased intracellular free Ca²⁺ levels trigger other components of the insulin secretion pathway to release granules at or near the plasma membrane (Figure 1). Mutations in the KCNJ11 gene can cause Diabetes mellitus (DM), because of the reduced ability of ATP to inhibit the activity of the KATP channel and the enhanced ability of Mg_ATP to simultaneously stimulate the function of this channel. This is associated with defective insulin secretion, ultimately causing DM. Type 2 diabetes (T2D) is a multifactorial disease with susceptibility of several genes. KCNJ11 gene encodes ATP‑sensitive potassium channel subunits. Some studies suggested that KCNJ11 (E23K) mutation increases the risk of T2D.

Figure1. Mechanism of insulin secretion by the KATP channel in pancreatic beta cells

KCNJ11 common polymorphisms are involved in diabetes. KCNJ11 has 219 SNPs, six of which have been receiving more attention for their association with diabetes. Among these six common SNPs, three are located in the coding regions and three in the noncoding regions. These six SNPs include rs5219, rs5215, rs5210, rs5218, rs886288, and rs2285676.

References:

Haghvirdizadeh P, et al. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus. Journal of Diabetes Research, 2015,(2015-9-13).
Rastegari A, et al. Association of KCNJ11 (E23K) gene polymorphism with susceptibility to type 2 diabetes in Iranian patients. Adv Biomed Res, 2015, 4(1):1.
Ioannou Y S, et al. KCNJ11 activating mutations cause both transient and permanent neonatal diabetes mellitus in Cypriot patients. Pediatric Diabetes, 2015, 12(2):133-137.

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