TRPM4 Gene: Transient Receptor Potential Cation Channel Subfamily M Member 4
A calcium-activated non-selective cation channel involved in cardiac conduction, immune response, and cancer
Gene Information Card
| Symbol | TRPM4 |
|---|---|
| Full Name | Transient Receptor Potential Cation Channel Subfamily M Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 54795 ncbi.nlm.nih.gov/gene/54795 |
| Ensembl ID | ENSG00000130529 |
| UniProt ID | Q9HCC0 |
| OMIM ID | 606936 |
| HGNC ID | 17993 |
| Aliases | EPM, LTrpC4, TRPM4B, PFHB1B |
Description
TRPM4 encodes a calcium-activated non-selective cation channel that is permeable to monovalent cations such as Na+ and K+ but not to Ca2+. It is widely expressed in cardiac tissue, immune cells, and various epithelia. The channel is involved in regulating membrane potential, calcium signaling, and cell volume. Mutations in TRPM4 are associated with cardiac conduction disorders, including progressive familial heart block type IB (PFHB1B) and Brugada syndrome. Altered expression has also been reported in several cancers and immune-related conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive familial heart block type IB (PFHB1B) | Loss-of-function mutations reduce channel activity, impairing cardiac conduction | OMIM #604559; ClinVar |
| Brugada syndrome | Gain-of-function mutations increase channel activity, leading to altered action potential duration | OMIM #601144; ClinVar |
| Isolated cardiac conduction disease | Missense variants disrupt channel gating or trafficking | ClinVar; NCBI |
| Cancer (prostate, colorectal, breast) | Overexpression promotes cell proliferation and migration via calcium signaling | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Skeletal muscle | 8.7 | Low |
| Brain | 6.2 | Low |
| Lung | 4.1 | Low |
| Kidney | 3.5 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.4 | High expression; used for functional studies |
| K562 (leukemia) | 9.8 | Moderate expression |
| HeLa (cervical cancer) | 7.3 | Moderate expression |
| MCF7 (breast cancer) | 5.1 | Low expression |
| Jurkat (T-cell leukemia) | 12.1 | High expression; relevant for immune function |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly555Arg | Missense | Rare | Gain-of-function; associated with Brugada syndrome |
| p.Arg164Trp | Missense | Rare | Loss-of-function; associated with PFHB1B |
| p.Glu7Lys | Missense | Rare | Loss-of-function; reduced channel expression |
| p.Ala432Thr | Missense | Rare | Gain-of-function; altered voltage dependence |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg164Trp and p.Glu7Lys reduce channel activity or surface expression, leading to cardiac conduction defects (PFHB1B).
Gain of Function (GOF)
Mutations such as p.Gly555Arg and p.Ala432Thr increase channel activity, contributing to Brugada syndrome by shortening action potential duration.
Dominant Negative (DN)
No well-characterized dominant-negative mutations have been reported for TRPM4.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005222 - intracellularly calcium-activated cation channel activity | • GO:0005515 - protein binding |
| • GO:0005886 - plasma membrane | • GO:0016021 - integral component of membrane |
| • GO:0070588 - calcium ion transmembrane transport | • GO:0034220 - ion transmembrane transport |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Cardiac conduction (Reactome: R-HSA-5576891)
• Ion channel transport (Reactome: R-HSA-983712)
Protein Summary
TRPM4 is a 1214-amino acid protein with six transmembrane domains, forming a calcium-activated non-selective cation channel. It is activated by intracellular Ca2+ and modulated by ATP, PIP2, and voltage. The channel is critical for regulating membrane depolarization in cardiac myocytes, pancreatic beta cells, and immune cells. Alternative splicing generates isoforms with distinct functional properties. Post-translational modifications include N-glycosylation and phosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPM4 Knockout HEK293 Cell Line | EDJ-KQ1064 | Human | 54795 | Details Get a Quote |
| TRPM4 Knockout HCT 116 Cell Line | EDJ-KQ20193 | Human | 54795 | Details Get a Quote |
| TRPM4 Knockout HeLa Cell Line | EDJ-KQ20194 | Human | 54795 | Details Get a Quote |
| TRPM4 Knockout A-549 Cell Line | EDJ-KQ18845 | Human | 54795 | Details Get a Quote |
| TRPM4 Knockout U-118MG Cell Line | EDC90254 | Human | 54795 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
