Encyclopedia
Transient receptor potential cation channel subfamily M member 4: The TRPM4 gene provides instructions for making a protein called transient receptor potential cation channel subfamily M member 4 (TRPM4).
- genes
1. 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.
2. Health Conditions Related to Genetic Changes
2.1. 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.
Brugada syndrome
3. Other 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
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/trpm4
References
- Abriel H, Syam N, Sottas V, Amarouch MY, Rougier JS. TRPM4 channels in thecardiovascular system: physiology, pathophysiology, and pharmacology. BiochemPharmacol. 2012 Oct 1;84(7):873-81. doi: 10.1016/j.bcp.2012.06.021.
- Kruse M, Pongs O. TRPM4 channels in the cardiovascular system. Curr OpinPharmacol. 2014 Apr;15:68-73. doi: 10.1016/j.coph.2013.12.003.Review.
- 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 ionchannel TRPM4 is associated with human progressive familial heart block type I. JClin Invest. 2009 Sep;119(9):2737-44. doi: 10.1172/JCI38292.
- Stallmeyer B, Zumhagen S, Denjoy I, Duthoit G, Hébert JL, Ferrer X, MaugenreS, Schmitz W, Kirchhefer U, Schulze-Bahr E, Guicheney P, Schulze-Bahr E.Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 inpatients with cardiac conductance disturbances. Hum Mutat. 2012 Jan;33(1):109-17.doi: 10.1002/humu.21599.
