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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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TRPM4
transient receptor potential cation channel subfamily M member 4
Chromosome 19 Β· 19q13.33
NCBI Gene: 54795Ensembl: ENSG00000130529.17HGNC: HGNC:17993UniProt: B4DIX5
114PubMed Papers
22Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of ventricular cardiac muscle cell action potentialcalcium-activated cation channel activitycalcium ion bindingprotein bindingFamilial progressive cardiac conduction defecterythrokeratodermia variabilisAbnormality of the cardiovascular systemBrugada syndrome
✦AI Summary

TRPM4 is a calcium-activated, non-selective cation channel that is impermeable to calcium but allows sodium and potassium influx upon activation 1. The channel is activated by increased intracellular calcium and regulated by temperature and PIP2, leading to membrane depolarization through sodium entry 1. TRPM4 is widely expressed throughout the body and plays crucial roles in cardiac conduction, with gain-of-function mutations causing familial cardiac conduction disorders 12. The channel exhibits temperature sensitivity, with activity dramatically potentiated by temperature increases 3. In pathological conditions, persistent TRPM4 activation can trigger necrotic cell death through sodium overload 4. TRPM4 physically couples with NMDA receptors, contributing to excitotoxicity in neurological conditions, and disrupting this interaction provides neuroprotection in stroke and retinal degeneration models 5. The channel is increasingly recognized in cancer biology, where overexpression contributes to proliferation, migration, and cell cycle progression in various cancers including prostate, colorectal, and B-cell lymphoma 67. TRPM4's role in disrupting calcium homeostasis makes it a potential therapeutic target for both neurological diseases and cancer metastasis 6.

Sources cited
1
TRPM4 is a Ca2+-activated nonselective cation channel that allows Na+ entry but is impermeable to Ca2+
PMID: 24756717
2
TRPM4 is a monovalent cation-selective channel involved in cardiac rhythm regulation
PMID: 37853091
3
TRPM4 activity is drastically potentiated by temperature increase
PMID: 39294615
4
Persistent TRPM4 activation triggers necrotic cell death through sodium overload
PMID: 39915626
5
TRPM4 physically couples with NMDA receptors and contributes to excitotoxicity
PMID: 33033186
6
TRPM4 is overexpressed in various cancers and contributes to proliferation and migration
PMID: 33562811
7
TRPM4 expression mediates cancer cell migration and invasion behaviors
PMID: 30980865
Disease Associationsβ“˜22
Familial progressive cardiac conduction defectOpen Targets
0.79Strong
erythrokeratodermia variabilisOpen Targets
0.65Moderate
Abnormality of the cardiovascular systemOpen Targets
0.34Weak
Brugada syndromeOpen Targets
0.18Weak
Prolonged QT intervalOpen Targets
0.18Weak
hypertrophic cardiomyopathyOpen Targets
0.16Weak
cardiomyopathyOpen Targets
0.15Weak
progressive familial heart blockOpen Targets
0.15Weak
progressive familial heart block, type 1AOpen Targets
0.15Weak
genetic disorderOpen Targets
0.15Weak
sudden cardiac arrestOpen Targets
0.15Weak
dilated cardiomyopathyOpen Targets
0.12Weak
arrhythmogenic right ventricular cardiomyopathyOpen Targets
0.12Weak
cardiac arrestOpen Targets
0.12Weak
catecholaminergic polymorphic ventricular tachycardia 1Open Targets
0.12Weak
conduction system disorderOpen Targets
0.12Weak
ventricular fibrillationOpen Targets
0.11Weak
myoepithelial tumorOpen Targets
0.11Weak
short QT syndromeOpen Targets
0.11Weak
Wolff-Parkinson-White SyndromeOpen Targets
0.11Weak
Erythrokeratodermia variabilis et progressiva 6UniProt
Progressive familial heart block 1BUniProt
Pathogenic Variants7
NM_017636.4(TRPM4):c.3119T>C (p.Ile1040Thr)Pathogenic
Erythrokeratodermia variabilis et progressiva 6|Progressive familial heart block type IB|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1040
NM_017636.4(TRPM4):c.1127T>C (p.Ile376Thr)Pathogenic
Progressive familial heart block type IB|Cardiovascular phenotype|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 376
NM_017636.4(TRPM4):c.273C>T (p.Leu91=)Likely pathogenic
Exertional Heat Illness
β˜…β˜†β˜†β˜†2024β†’ Residue 91
NM_017636.4(TRPM4):c.19G>A (p.Glu7Lys)Likely pathogenic
Progressive familial heart block type IB|TRPM4-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 7
NM_017636.4(TRPM4):c.448G>T (p.Gly150Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 150
NM_017636.4(TRPM4):c.3099C>G (p.Ile1033Met)Pathogenic
Erythrokeratodermia variabilis et progressiva 6
β˜†β˜†β˜†β˜†2019β†’ Residue 1033
NM_017636.4(TRPM4):c.2741A>G (p.Lys914Arg)Pathogenic
Progressive familial heart block type IB
β˜†β˜†β˜†β˜†2012β†’ Residue 914
View on ClinVar β†—
Related Genes
ABCC8Protein interaction99%SCN5AProtein interaction95%TRPC3Protein interaction94%NUDT9Protein interaction92%SCN3BProtein interaction88%SCN2BProtein interaction88%
Tissue Expression6 tissues
Lung
100%
Heart
71%
Liver
57%
Ovary
15%
Brain
8%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
TRPM4ABCC8SCN5ATRPC3NUDT9SCN3BSCN2B
PROTEIN STRUCTURE
Preparing viewer…
PDB9B8X Β· 3.00 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.08LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.93 [0.81–1.08]
RankingsWhere TRPM4 stands among ~20K protein-coding genes
  • #4,173of 20,598
    Most Researched114 Β· top quartile
  • #3,179of 5,498
    Most Pathogenic Variants7
  • #11,023of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedTRPM4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Persistent activation of TRPM4 triggers necrotic cell death characterized by sodium overload.
PMID: 39915626
Nat Chem Biol Β· 2025
1.00
2
TRPM channels in health and disease.
PMID: 37853091
Nat Rev Nephrol Β· 2024
0.90
3
TRPM4.
PMID: 24756717
Handb Exp Pharmacol Β· 2014
0.80
4
Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants.
PMID: 33033186
Science Β· 2020
0.70
5
TRPM4 channel and cancer.
PMID: 30980865
Cancer Lett Β· 2019
0.60