Alternative titles; symbols
HGNC Approved Gene Symbol: KCNJ12
Cytogenetic location: 17p11.2 Genomic coordinates (GRCh38): 17:21,376,357-21,419,870 (from NCBI)
By RT-PCR of human atrial RNA using primers based on the conserved transmembrane domains of inwardly rectifying K(+) channel (Kir or IRK; see 602208) family proteins, Wible et al. (1995) isolated a Kir family member from a human atrial cDNA library. The heart IRK predicted 432-amino acid sequence is 98% identical to that of rat RB-IRK2. Northern blot analysis showed that the gene was expressed in human ventricle and atrium.
Namba et al. (1997) cloned the KCNJ12 gene from a human genomic library.
Using Northern blot analysis, Ryan et al. (2010) detected an approximately 2.2-kb Kcnj12 transcript that was highly expressed in skeletal muscle, but not in any other tissue examined, including heart.
Wible et al. (1995) demonstrated that human heart IRK functions as an inward rectifier channel when heterologously expressed in Xenopus oocytes.
Crystal Structure
Tao et al. (2009) presented the crystal structure of Kir2.2 from chicken, which, excluding the unstructured amino and carboxyl termini, is 90% identical to human Kir2.2. Crystals containing rubidium, strontium, and europium revealed binding sites along the ion conduction pathway that are both conductive and inhibitory. The sites correlated with extensive electrophysiologic data and provided a structural basis for understanding rectification. The channel's extracellular surface, with large structured turrets and an unusual selectivity filter entryway, might explain the relative insensitivity of eukaryotic inward rectifiers to toxins.
Ryan et al. (2010) determined that the KCNJ12 gene contains 3 exons, with the entire coding region located within exon 3.
Hugnot et al. (1997) mapped the KCNJ12 gene to 17p11.1 by fluorescence in situ hybridization. Namba et al. (1997) used fluorescence in situ hybridization to show that the KCNJ12 gene maps to chromosome 17p11.2-p11.1.
Hugnot, J. P., Pedeutour, F., Le Calvez, C., Grosgeorge, J., Passage, E., Fontes, M., Lazdunski, M. The human inward rectifying K(+) channel Kir 2.2 (KCNJ12) gene: gene structure, assignment to chromosome 17p11.1, and identification of a simple tandem repeat polymorphism. Genomics 39: 113-116, 1997. [PubMed: 9027495] [Full Text: https://doi.org/10.1006/geno.1996.4450]
Namba, N., Mori, R., Tanaka, H., Kondo, I., Narahara, K., Seino, Y. The inwardly rectifying potassium channel subunit Kir2.2v (KCNJN1) maps to 17p11.2-p11.1. Cytogenet. Cell Genet. 79: 85-87, 1997. [PubMed: 9533018] [Full Text: https://doi.org/10.1159/000134688]
Ryan, D. P., da Silva, M. R. D., Soong, T. W., Fontaine, B., Donaldson, M. R., Kung, A. W. C., Jongjaroenprasert, W., Liang, M. C., Khoo, D. H. C., Cheah, J. S., Ho, S. C., Bernstein, H. S., Maciel, R. M. B., Brown, R. H., Jr., Ptacek, L. J. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell 140: 88-98, 2010. [PubMed: 20074522] [Full Text: https://doi.org/10.1016/j.cell.2009.12.024]
Tao, X., Avalos, J. L., Chen, J., MacKinnon, R. Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1-angstrom resolution. Science 326: 1668-1674, 2009. [PubMed: 20019282] [Full Text: https://doi.org/10.1126/science.1180310]
Wible, B. A., De Biasi, M., Majumder, K., Taglialatela, M., Brown, A. M. Cloning and functional expression of an inwardly rectifying K(+) channel from human atrium. Circ. Res. 76: 343-350, 1995. [PubMed: 7859381] [Full Text: https://doi.org/10.1161/01.res.76.3.343]