Normal Function
The KCNK9 gene provides instructions for making a protein called TASK3, which functions as a potassium channel. Potassium channels transport positively charged atoms (ions) of potassium into and out of cells.
TASK3 channels are found throughout the body. They are especially abundant in nerve cells (neurons) in the brain, particularly the region of the brain that coordinates movement (cerebellum). The flow of ions through potassium channels in neurons is involved in activating (exciting) the neurons and sending electrical signals in the brain. Unlike some potassium channels that open and close in response to certain triggers, TASK3 channels are always open, although their activity can be controlled by the environment surrounding the cell. Because the channels are always open, they are often called background or leak channels. TASK3 channels maintain the cell's ability to generate electrical signals and regulate the activity (excitability) of cells. These channels also appear to play a role in the movement (migration) of certain neurons in the brain.
People inherit two copies of their genes, one from their mother and one from their father. Usually both copies of each gene are active, or "turned on," in cells. For some genes, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person's father; others are active only when inherited from a person's mother. This phenomenon is known as genomic imprinting. The KCNK9 gene is a maternally expressed imprinted gene, which means that only the copy of the gene that comes from the mother is active. The copy of the gene that comes from the father is turned off (silenced).
Health Conditions Related to Genetic Changes
KCNK9 imprinting syndrome
At least two changes in the KCNK9 gene, both of which have the same effect on the TASK3 channel protein, have been found to cause KCNK9 imprinting syndrome. This condition is characterized by weak muscle tone (hypotonia) from birth that can affect the ability to eat. Affected individuals typically have intellectual disability and delayed development of speech and motor skills, such as walking. Because the copy of the KCNK9 gene from the father is silenced, the condition occurs only when there is a mutation in the copy of the gene inherited from the mother.
The gene mutations that cause KCNK9 imprinting syndrome change a single protein building block (amino acid) in the TASK3 channel; the amino acid arginine replaces the amino acid glycine at position 236 (written as Gly236Arg or G236R). This alteration reduces the flow of ions through TASK3 channels by 80 percent. Research suggests that certain neurons with altered TASK3 channels are unable to repeatedly generate electrical signals. The reduction of ion transport through TASK3 channels disrupts normal neuron development and excitability. Impairment of neuron function likely underlies the hypotonia, intellectual disability, and developmental problems characteristic of KCNK9 imprinting syndrome.
More About This Health ConditionOther Names for This Gene
- acid-sensitive potassium channel protein TASK-3
- K2p9.1
- KT3.2
- potassium channel subfamily K member 9
- potassium channel, two pore domain subfamily K, member 9
- TASK-3
- TASK3
- TWIK-related acid-sensitive K(+) channel 3
- two pore K(+) channel KT3.2
- two pore potassium channel KT3.2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bando Y, Hirano T, Tagawa Y. Dysfunction of KCNK potassium channels impairs neuronal migration in the developing mouse cerebral cortex. Cereb Cortex. 2014 Apr;24(4):1017-29. doi: 10.1093/cercor/bhs387. Epub 2012 Dec 12. Citation on PubMed
- Barel O, Shalev SA, Ofir R, Cohen A, Zlotogora J, Shorer Z, Mazor G, Finer G, Khateeb S, Zilberberg N, Birk OS. Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9. Am J Hum Genet. 2008 Aug;83(2):193-9. doi: 10.1016/j.ajhg.2008.07.010. Citation on PubMed or Free article on PubMed Central
- Enyedi P, Czirjak G. Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol Rev. 2010 Apr;90(2):559-605. doi: 10.1152/physrev.00029.2009. Citation on PubMed
- Graham JM Jr, Zadeh N, Kelley M, Tan ES, Liew W, Tan V, Deardorff MA, Wilson GN, Sagi-Dain L, Shalev SA. KCNK9 imprinting syndrome-further delineation of a possible treatable disorder. Am J Med Genet A. 2016 Oct;170(10):2632-7. doi: 10.1002/ajmg.a.37740. Epub 2016 May 6. Citation on PubMed
- Molecular Biology of the Cell (fourth edition, 2002): The Membrane Potential in Animal Cells Depends Mainly on K+ Leak Channels and the K+ Gradient Across the Plasma Membrane
- Veale EL, Hassan M, Walsh Y, Al-Moubarak E, Mathie A. Recovery of current through mutated TASK3 potassium channels underlying Birk Barel syndrome. Mol Pharmacol. 2014 Mar;85(3):397-407. doi: 10.1124/mol.113.090530. Epub 2013 Dec 16. Citation on PubMed
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