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  3. TRPM6

TRPM6 (Transient receptor potential cation channel subfamily M member 6)

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Summary of TRPM6

Essential ion channel and serine/threonine-protein kinase. Crucial for magnesium homeostasis. Has an important role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Isoforms of the type M6-kinase lack the ion channel region.

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Protein names

Recommended name:

Transient receptor potential cation channel subfamily M member 6

Alternative name(s):

Channel kinase 2
Melastatin-related TRP cation channel 6

TRPM6 SNPs

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  1. RS11144134 (TRPM6) ??
  2. RS113607577 (TRPM6) ??
  3. RS144773862 (TRPM6) ??
  4. RS2274924 (TRPM6) ??
  5. RS35804026 (TRPM6) ??
  6. RS3750425 (TRPM6) ??
  7. RS514209 (TRPM6) ??

Top Gene-Substance Interactions

Substances That Increase TRPM6

Substances Interaction Organism Category

Substances That Decrease TRPM6

Substances Interaction Organism Category

Advanced Summary

Hypomagnesemia with secondary hypocalcemia At least 38 mutations in the TRPM6 gene has been found to cause hypomagnesemia with secondary hypocalcemia. This condition is characterized by low levels of magnesium (hypomagnesemia) and calcium (hypocalcemia) in the body, which leads to neurological problems that begin in infancy, including muscle spasms and seizures. TRPM6 gene mutations result in a lack of functional protein. Nonfunctional TRPM6 channels prevent Mg2+ absorption in the intestine and cause too much Mg2+ to be released in the urine. A lack of Mg2+ in the blood impairs the production of parathyroid hormone, which likely reduces blood Ca2+ levels. Additionally, hypomagnesemia and hypocalcemia can disrupt many cell processes and impair the function of motor neurons, leading to neurological problems and movement disorders characteristic of this condition. If the condition is not effectively treated and low Mg2+ levels persist, signs and symptoms can worsen over time and may lead to early death.

The TRPM6 gene provides instructions for making a protein that acts as a channel, which allows charged atoms (ions) of magnesium (Mg2+) to flow into cells; the channel may also allow small amounts of calcium ions (Ca2+) to pass through cells. Magnesium is involved in many cell processes, including the production of cellular energy, maintenance of DNA building blocks (nucleotides), protein production, and cell growth and death. Additionally, Mg2+ is needed for the production of a substance called parathyroid hormone that regulates blood calcium levels. Magnesium and calcium are also required for the normal functioning of nerve cells that control muscle movement (motor neurons). The TRPM6 channel is embedded in the membrane of epithelial cells that line the large intestine, structures in the kidneys known as distal convoluted tubules, the lungs, and the testes in males. When the body needs additional Mg2+, the TRPM6 channel allows it to be absorbed in the intestine and filtered from the fluids that pass through the kidneys by the distal convoluted tubules. When the body has sufficient or too much Mg2+, the TRPM6 channel does not filter out the Mg2+ from fluids but allows the ion to be released from the kidney cells into the urine. The channel also helps to regulate Ca2+ but to a lesser degree.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • c-Fos

Tissue specificity:

Highly expressed in kidney and colon. Isoform TRPM6a and isoform TRPM6b, are coexpressed with TRPM7 in kidney, and testis, and are also found in several cell lines of lung origin. Isoform TRPM6c is detected only in testis and in NCI-H510A small cell lung carcinoma cells.

Gene Pathways:

  • Transmembrane transport of small molecules
  • Mineral absorption

Molecular Function:

  • Atp Binding
  • Calcium Channel Activity
  • Metal Ion Binding
  • Protein Serine/Threonine Kinase Activity

Biological Processes:

  • Calcium Ion Transmembrane Transport
  • Protein Tetramerization
  • Response To Toxic Substance
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| Transient receptor potential cation channel subfamily M member 1| transient receptor potential cation channel, subfamily M, member 6| trpm6| A306_12052| Anapl_07542| AS27_02951| AS28_10924| CHAK2| channel kinase 2| D623_10034415| HMGX| HOMG| HOMG1| HSH| M91_08001| melastatin-related TRP cation channel 6| N300_09200| N301_11850| N302_05748| N305_12189| N306_02597| N307_14310| N308_04130| N310_06316| N312_07996| N324_00702| N325_04134| N327_12197| N328_00760| N330_00698| N335_04968| N339_11651| N340_10328| N341_05970| PAL_GLEAN10021098| PANDA_014043| transient receptor potential cation channel 6/channel-kinase 2| transient receptor potential cation channel, subfamily M, member 7| Transient receptor potential cation channel subfamily M member 7| transient receptor potential melastatin 6| Transient receptor putative cation channel subfamily M member 6| TREES_T100020742| TRPM6/CHAK2| TRPM7| UY3_12428| Y1Q_003537| Y956_00240| Z169_08582

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