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26 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TRPM7
transient receptor potential cation channel subfamily M member 7
Chromosome 15 · 15q21.2
NCBI Gene: 54822Ensembl: ENSG00000092439.16HGNC: HGNC:17994UniProt: H0YLN8
248PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelKinaseTransporter
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
magnesium ion transportcalcium channel activitymagnesium ion transmembrane transporter activitynecroptotic processintestinal hypomagnesemia 1amyotrophic lateral sclerosis-parkinsonism-dementia complexautosomal dominant macrothrombocytopenianeuroinflammatory disorder
✦AI Summary

TRPM7 is a ubiquitously expressed chanzyme—a fusion protein combining an ion channel and kinase domain—that functions as a critical regulator of divalent cation homeostasis and cellular signaling 1. As an ion channel, TRPM7 transports Mg2+, Ca2+, and Zn2+ across the plasma membrane, with particular prominence in magnesium homeostasis 2. The channel's kinase domain can be proteolytically cleaved from the channel segment in a cell-type-specific manner; in immune cells, caspase-mediated cleavage releases TRPM7-cleaved kinase fragments that translocate to the nucleus and phosphorylate histone residues involved in cell differentiation 3. TRPM7 participates in diverse pathophysiological processes including embryonic development, cardiovascular disease, and immunity 1. Recent evidence demonstrates TRPM7's involvement in pyroptosis during status epilepticus through a p-STAT3/TRPM7/Zn2+ positive feedback loop 4, and in rheumatoid arthritis-associated chondrocyte ferroptosis via the PKCα-NOX4 axis 5. In cancer, TRPM7 silencing shifts ovarian cancer metabolism from glycolysis to oxidative phosphorylation by enhancing AMPK activation and HIF-1α degradation 6. TRPM7 also mediates macrophage immunoregulation through mitochondrial transfer in testicular tissue homeostasis 7. These multifaceted roles position TRPM7 as a promising therapeutic target across neurological, inflammatory, and malignant diseases.

Sources cited
1
TRPM7 is highly permeable to divalent cations (Ca2+, Mg2+, Zn2+) and functions as a cellular sensor in mineral homeostasis and immunity
PMID: 37853091
2
TRPM7 is a ubiquitously expressed channel kinase with prominent roles in magnesium homeostasis, embryonic development, cardiovascular disease, and cancer
PMID: 24756720
3
TRPM7 contributes to pyroptosis in status epilepticus through the p-STAT3/TRPM7/Zn2+ signaling pathway
PMID: 39617893
4
TRPM7 kinase domain is cleaved and accumulates in the nucleus where it phosphorylates histone H3 at serine 10 to regulate inflammatory cytokine expression
PMID: 34001887
5
TRPM7 channel inhibition attenuates rheumatoid arthritis chondrocyte ferroptosis by suppressing the PKCα-NOX4 axis
PMID: 35917680
6
TRPM7 silencing inhibits ovarian cancer growth by enhancing AMPK activation to promote HIF-1α degradation and shift metabolism from glycolysis to oxidative phosphorylation
PMID: 35101076
7
TRPM7 is a chanzyme with ubiquitous expression that interacts with growth factor signaling through receptor tyrosine kinases
PMID: 30995736
8
TRPM7 mediates mitochondrial transfer from stem Leydig cells to macrophages in a TRPM7-dependent manner to support immunological homeostasis
PMID: 38459012
Disease Associationsⓘ21
intestinal hypomagnesemia 1Open Targets
0.42Moderate
amyotrophic lateral sclerosis-parkinsonism-dementia complexOpen Targets
0.42Moderate
autosomal dominant macrothrombocytopeniaOpen Targets
0.38Weak
neuroinflammatory disorderOpen Targets
0.31Weak
MacrothrombocytopeniaOpen Targets
0.19Weak
macrothrombocytopenia, isolatedOpen Targets
0.18Weak
Ischemic strokeOpen Targets
0.15Weak
coronary artery diseaseOpen Targets
0.14Weak
juvenile amyotrophic lateral sclerosisOpen Targets
0.12Weak
gliomaOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Weak
ovarian cancerOpen Targets
0.10Suggestive
prostate cancerOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
pancreatic adenocarcinomaOpen Targets
0.09Suggestive
neuroblastomaOpen Targets
0.09Suggestive
chronic fatigue syndromeOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.08Suggestive
pulmonary arterial hypertensionOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1UniProt
Pathogenic Variants4
NM_017672.6(TRPM7):c.2999T>C (p.Met1000Thr)Pathogenic
See cases
★☆☆☆2023→ Residue 1000
NM_017672.6(TRPM7):c.3242T>G (p.Leu1081Arg)Pathogenic
See cases
★☆☆☆2023→ Residue 1081
NM_017672.6(TRPM7):c.3+1G>CPathogenic
Intestinal hypomagnesemia 1
☆☆☆☆2021
NM_017672.6(TRPM7):c.3137G>A (p.Gly1046Asp)Pathogenic
Intestinal hypomagnesemia 1
☆☆☆☆→ Residue 1046
View on ClinVar ↗
Related Genes
TRPM2Protein interaction98%MLKLProtein interaction93%SLC41A1Protein interaction80%PLCB1Protein interaction79%TRPC1Protein interaction75%TRPV1Protein interaction75%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
96%
Liver
81%
Ovary
63%
Lung
49%
Brain
20%
Gene Interaction Network
Click a node to explore
TRPM7TRPM2MLKLSLC41A1PLCB1TRPC1TRPV1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96QT4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.68LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.58 [0.49–0.68]
RankingsWhere TRPM7 stands among ~20K protein-coding genes
  • #1,561of 20,598
    Most Researched248 · top 10%
  • #3,692of 5,498
    Most Pathogenic Variants4
  • #5,067of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedTRPM7
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
TRPM channels in health and disease.
PMID: 37853091
Nat Rev Nephrol · 2024
1.00
2
TRPM7.
PMID: 24756720
Handb Exp Pharmacol · 2014
0.90
3
TRPM7 contributes to pyroptosis and its involvement in status epilepticus.
PMID: 39617893
J Neuroinflammation · 2024
0.80
4
TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration.
PMID: 34001887
Nat Commun · 2021
0.70
5
Magnesium reabsorption in the kidney.
PMID: 36633869
Am J Physiol Renal Physiol · 2023
0.64