TRPM6 Gene: Transient Receptor Potential Cation Channel Subfamily M Member 6
Key regulator of magnesium homeostasis and epithelial ion transport
Gene Information Card
| Symbol | TRPM6 |
|---|---|
| Full Name | Transient Receptor Potential Cation Channel Subfamily M Member 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.13 |
| NCBI Gene ID | 140803 ncbi.nlm.nih.gov/gene/140803 |
| Ensembl ID | ENSG00000019186 |
| UniProt ID | Q9BX84 |
| OMIM ID | 607009 |
| HGNC ID | 17996 |
| Aliases | CHAK2, HOMG1, HOMG5, LPRP5, TRP-PLIK2 |
Description
TRPM6 encodes a member of the transient receptor potential (TRP) family, subfamily M. The protein functions as a calcium-permeable cation channel with a kinase domain, essential for magnesium reabsorption in the kidney and intestine. Mutations cause hypomagnesemia with secondary hypocalcemia (HSH).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypomagnesemia with secondary hypocalcemia (HSH) | Loss-of-function mutations impair TRPM6-mediated Mg2+ reabsorption in renal distal tubules and intestinal epithelium, leading to severe Mg2+ deficiency and secondary hypocalcemia. | OMIM #602014; multiple familial cases with biallelic TRPM6 variants |
| Preeclampsia | Reduced TRPM6 expression in placental trophoblasts may contribute to maternal hypomagnesemia and endothelial dysfunction. | ClinVar; case-control studies show association with TRPM6 polymorphisms |
| Type 2 diabetes | TRPM6 variants linked to altered magnesium homeostasis, which influences insulin sensitivity and glucose metabolism. | GWAS catalog; meta-analyses of European cohorts |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Small intestine | 8.3 | Medium |
| Colon | 6.1 | Low |
| Lung | 2.4 | Low |
| Brain | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK-293 | 15.2 | High expression in recombinant systems |
| Caco-2 | 9.7 | Intestinal epithelial model |
| HK-2 | 11.4 | Proximal tubule cell line |
| BeWo | 7.8 | Placental trophoblast model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3179G>A (p.Arg1060His) | Missense | Rare (0.0002 in gnomAD) | Loss of channel function; associated with HSH |
| c.4423C>T (p.Arg1475*) | Nonsense | Rare (0.0001 in gnomAD) | Premature truncation; complete loss of function |
| c.1795C>T (p.Arg599Trp) | Missense | Rare (0.0003 in gnomAD) | Impaired Mg2+ permeability; HSH phenotype |
| c.2668+1G>A | Splice donor | Rare (0.00005 in gnomAD) | Exon skipping; loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Most TRPM6 disease-associated mutations are loss-of-function, reducing or abolishing Mg2+ channel activity and kinase function, leading to hypomagnesemia.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TRPM6; such variants would be predicted to cause hypermagnesemia or related disorders.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg1060His) may exert dominant-negative effects when co-expressed with wild-type TRPM6, though autosomal recessive inheritance is typical.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Magnesium absorption (Reactome: R-HSA-4420097)
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• TRP channel regulation (KEGG: hsa04750)
Protein Summary
TRPM6 is a 1,975-amino acid protein with six transmembrane domains and a C-terminal alpha-kinase domain. It forms functional channels as homotetramers or heterotetramers with TRPM7. The channel is permeable to Mg2+ and Ca2+, and its kinase domain autophosphorylates and regulates channel activity. TRPM6 is critical for epithelial Mg2+ absorption in kidney and intestine.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRPM6 Knockout HEK293 Cell Line | EDJ-KQ2636 | Human | 140803 | Details Get a Quote |
| TRPM6 Knockout A-549 Cell Line | EDJ-KQ18197 | Human | 140803 | Details Get a Quote |
| TRPM6 Knockout HeLa Cell Line | EDJ-KQ18199 | Human | 140803 | Details Get a Quote |
| TRPM6 Knockout HCT 116 Cell Line | EDJ-KQ75346 | Human | 140803 | Details Get a Quote |
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