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    Topic review

    KCNA1 Gene

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    Submitted by: Dean Liu
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    Potassium voltage-gated channel subfamily A member 1

    1. Introduction

    The KCNA1 gene belongs to a large family of genes that provide instructions for making potassium channels. These channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.

    The KCNA1 gene provides instructions for making one part (the alpha subunit) of a potassium channel called Kv1.1. These channels are found in the brain, where they transport potassium ions into nerve cells (neurons). The flow of certain ions, including potassium, into and out of neurons regulates communication between these cells.

    2. Health Conditions Related to Genetic Changes

    2.1. Episodic Ataxia

    At least 20 mutations in the KCNA1 gene have been identified in people with episodic ataxia type 1 (EA1). People with this form of the condition have brief, recurrent episodes of poor coordination and balance (ataxia). Between episodes, many affected individuals experience myokymia, a muscle abnormality that can cause involuntary muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.

    Most of the KCNA1 mutations responsible for episodic ataxia change single protein building blocks (amino acids) in the alpha subunit of the Kv1.1 channel. Some of these changes prevent the assembly of functional channels, while other mutations alter the channel's structure. When Kv1.1 channels are missing or abnormal, the flow of potassium ions into neurons is reduced. This decrease in potassium ions overexcites certain neurons in the brain, which disrupts normal communication between these cells. Although changes in signaling between neurons underlie the episodes of uncoordinated movement seen in people with episodic ataxia, it is unclear how altered potassium ion transport causes the specific features of the condition.

    2.2. Other disorders

    Mutations in the KCNA1 gene have been found to cause a range of signs and symptoms affecting the nervous system. In at least one family, isolated myokymia (continuous muscle twitching and spasms without episodes of ataxia) has been attributed to KCNA1 mutations. Changes in this gene have also been identified in a small number of people with epilepsy. Like the KCNA1 mutations that underlie episodic ataxia, the mutations that cause isolated myokymia and epilepsy reduce the flow of potassium ions through Kv1.1 channels, disrupting normal communication between neurons in the brain. Researchers are working to determine why mutations in this single gene can cause several different disorders of the nervous system.

    3. Other Names for This Gene

    • AEMK

    • EA1

    • HBK1

    • HUK1

    • KCNA1_HUMAN

    • KV1.1

    • MBK1

    • MGC126782

    • MGC138385

    • MK1

    • potassium channel, voltage gated shaker related subfamily A, member 1

    • potassium voltage-gated channel, shaker-related subfamily, member 1 (episodic ataxia with myokymia)

    • RBK1

    • voltage-gated potassium channel subunit Kv1.1

    This entry is adapted from https://medlineplus.gov/genetics/gene/kcna1

    References

    1. Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, Litt M. Episodicataxia/myokymia syndrome is associated with point mutations in the humanpotassium channel gene, KCNA1. Nat Genet. 1994 Oct;8(2):136-40.
    2. Chen H, von Hehn C, Kaczmarek LK, Ment LR, Pober BR, Hisama FM. Functionalanalysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia.Neurogenetics. 2007 Apr;8(2):131-5.
    3. Eunson LH, Rea R, Zuberi SM, Youroukos S, Panayiotopoulos CP, Liguori R, AvoniP, McWilliam RC, Stephenson JB, Hanna MG, Kullmann DM, Spauschus A. Clinical,genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol. 2000 Oct;48(4):647-56.
    4. Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW; CINCHinvestigators. Primary episodic ataxias: diagnosis, pathogenesis and treatment.Brain. 2007 Oct;130(Pt 10):2484-93.
    5. Maylie B, Bissonnette E, Virk M, Adelman JP, Maylie JG. Episodic ataxia type 1mutations in the human Kv1.1 potassium channel alter hKvbeta 1-induced N-typeinactivation. J Neurosci. 2002 Jun 15;22(12):4786-93.
    6. Rajakulendran S, Schorge S, Kullmann DM, Hanna MG. Episodic ataxia type 1: aneuronal potassium channelopathy. Neurotherapeutics. 2007 Apr;4(2):258-66.Review.
    7. Rea R, Spauschus A, Eunson LH, Hanna MG, Kullmann DM. Variable K(+) channelsubunit dysfunction in inherited mutations of KCNA1. J Physiol. 2002 Jan 1;538(Pt1):5-23.
    8. Zerr P, Adelman JP, Maylie J. Episodic ataxia mutations in Kv1.1 alterpotassium channel function by dominant negative effects or haploinsufficiency. J Neurosci. 1998 Apr 15;18(8):2842-8.
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