Encyclopedia
ankyrin 2. The ANK2 gene provides instructions for making a protein called ankyrin-B.
- genes
1. Normal Function
Ankyrin-B is part of a family of ankyrin proteins, which interact with many other types of proteins in cells throughout the body. Ankyrins help organize the cell's structural framework (the cytoskeleton) and link certain proteins that span the cell membrane to this framework. Additionally, ankyrins play key roles in important functions including cell movement (migration) and cell growth and division (proliferation).
The ankyrin-B protein is active in many cell types, particularly in the brain and in heart (cardiac) muscle. This protein mainly interacts with ion channels and ion transporters, which are complexes of proteins that move charged atoms (ions) across cell membranes. In the heart, the flow of ions (such as sodium, potassium, and calcium) through ion channels and ion transporters generates the electrical signals that control the heartbeat and maintain a normal heart rhythm. Ankyrin-B ensures these channels and transporters are in their proper locations in the cell membrane so they can regulate the flow of ions into and out of cardiac muscle cells. In addition, ankyrin-B helps ensure that signaling molecules that regulate the activity of ion channels and ion transporters are in the proper location.
2. Health Conditions Related to Genetic Changes
2.1. Ankyrin-B syndrome
At least ten mutations in the ANK2 gene have been found to cause ankyrin-B syndrome, a condition characterized by a variety of heart problems. Most often, mutations in the ANK2 gene lead to abnormalities of the heart's natural pacemaker (the sinoatrial node), a heart rate that is slower than normal (bradycardia), a disruption in the rhythm of the heart (arrhythmia), and an increased risk of fainting (syncope) and sudden death.
Each of the identified mutations in the ANK2 gene changes a single protein building block (amino acid) in the ankyrin-B protein. Most of these mutations alter a region of the ankyrin-B protein important for its function. At least one ANK2 gene mutation prevents ankyrin-B from getting to the cell membrane where it is needed to function. As a result of these genetic changes, the ankyrin-B protein cannot target ion channels and ion transporters to their correct locations in cardiac muscle cells. Although the channels and transporters are produced normally by the cell, they are unable to function if they are not inserted correctly into the cell membrane. This loss of functional channels and transporters in the heart disrupts the normal flow of ions, which alters the heart's normal rhythm and leads to the heart problems that can be a part of ankyrin-B syndrome.
2.2. Autism spectrum disorder
Autism spectrum disorder
3. Other Names for This Gene
- ANK2_HUMAN
- ankyrin 2, neuronal
- ankyrin B
- ankyrin, brain
- ankyrin, nonerythroid
- ankyrin-2, nonerythrocytic
- brank-2
- LQT4
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/ank2
References
- Alders M, Bikker H, Christiaans I. Long QT Syndrome. 2003 Feb 20 [updated 2018Feb 8]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1129/
- Chiang CE. Congenital and acquired long QT syndrome. Current concepts andmanagement. Cardiol Rev. 2004 Jul-Aug;12(4):222-34. Review.
- Cunha SR, Mohler PJ. Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line. J Biol Chem. 2008 Nov 14;283(46):31968-80. doi:10.1074/jbc.M806050200.
- Mohler PJ, Bennett V. Ankyrin-based cardiac arrhythmias: a new class ofchannelopathies due to loss of cellular targeting. Curr Opin Cardiol. 2005May;20(3):189-93. Review.
- Mohler PJ, Gramolini AO, Bennett V. Ankyrins. J Cell Sci. 2002 Apr 15;115(Pt8):1565-6.
- Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, DriskellIM, Schott JJ, Norris K, Leenhardt A, Kim RB, Escande D, Roden DM. Defining thecellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variantsassociated with clinical phenotypes display a spectrum of activities incardiomyocytes. Circulation. 2007 Jan 30;115(4):432-41.
- Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH, SongLS, Haurogné K, Kyndt F, Ali ME, Rogers TB, Lederer WJ, Escande D, Le Marec H,Bennett V. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and suddencardiac death. Nature. 2003 Feb 6;421(6923):634-9.
- Mohler PJ, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K, PrioriSG, Keating MT, Bennett V. A cardiac arrhythmia syndrome caused by loss ofankyrin-B function. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9137-42.
- Sherman J, Tester DJ, Ackerman MJ. Targeted mutational analysis of ankyrin-Bin 541 consecutive, unrelated patients referred for long QT syndrome genetictesting and 200 healthy subjects. Heart Rhythm. 2005 Nov;2(11):1218-23.
