Normal Function
The TRPM4 gene provides instructions for making a protein called transient receptor potential cation channel subfamily M member 4 (TRPM4). This protein acts as a channel, opening and closing at specific times to control the flow of positively charged atoms (cations) into and out of cells. The TRPM4 channel is embedded in the outer membrane of cells throughout the body, but it is abundant in heart (cardiac) cells and plays key roles in these cells' ability to generate and transmit electrical signals. TRPM4 channels play a major role in signaling the start of each heartbeat, coordinating the contractions of the upper and lower chambers of the heart, and maintaining a normal heart rhythm.
In addition to regulating electric signaling in the heart, the TRPM4 channel is important for the normal functioning of the immune system, the nervous system, the kidneys, and the pancreas.
Health Conditions Related to Genetic Changes
Progressive familial heart block
A few mutations in the TRPM4 gene have been found to cause progressive familial heart block. This condition alters the normal beating of the heart and can lead to fainting (syncope) or sudden cardiac arrest and death. The TRPM4 gene mutations change single protein building blocks (amino acids) in the TRPM4 channel. The altered channels have increased activity at the cell membrane, which likely alters the cell's ability to generate electrical signals because of the increased cation flow. Cardiac cells with these altered channels have difficulty producing and transmitting electrical signals that coordinate normal heartbeats. Interruption of this signaling causes heart block. Death of these impaired cardiac cells over time can lead to a buildup of scar tissue (fibrosis), worsening the heart block.
More About This Health ConditionBrugada syndrome
MedlinePlus Genetics provides information about Brugada syndrome
More About This Health ConditionOther Names for This Gene
- calcium-activated non-selective cation channel 1
- hTRPM4
- long transient receptor potential channel 4
- LTrpC4
- melastatin-4
- transient receptor potential cation channel, subfamily M, member 4
- TRPM4_HUMAN
- TRPM4B
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Abriel H, Syam N, Sottas V, Amarouch MY, Rougier JS. TRPM4 channels in the cardiovascular system: physiology, pathophysiology, and pharmacology. Biochem Pharmacol. 2012 Oct 1;84(7):873-81. doi: 10.1016/j.bcp.2012.06.021. Epub 2012 Jun 27. Citation on PubMed
- Kruse M, Pongs O. TRPM4 channels in the cardiovascular system. Curr Opin Pharmacol. 2014 Apr;15:68-73. doi: 10.1016/j.coph.2013.12.003. Epub 2013 Dec 25. Citation on PubMed
- Kruse M, Schulze-Bahr E, Corfield V, Beckmann A, Stallmeyer B, Kurtbay G, Ohmert I, Schulze-Bahr E, Brink P, Pongs O. Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I. J Clin Invest. 2009 Sep;119(9):2737-44. doi: 10.1172/JCI38292. Epub 2009 Aug 24. Citation on PubMed or Free article on PubMed Central
- Stallmeyer B, Zumhagen S, Denjoy I, Duthoit G, Hebert JL, Ferrer X, Maugenre S, Schmitz W, Kirchhefer U, Schulze-Bahr E, Guicheney P, Schulze-Bahr E. Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in patients with cardiac conductance disturbances. Hum Mutat. 2012 Jan;33(1):109-17. doi: 10.1002/humu.21599. Epub 2011 Oct 20. Citation on PubMed
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