The TRPM6 gene encodes a magnesium transporter expressed in enterocytes and renal tubular cells. Mutations of this gene cause autosomal recessive intestinal hypomagnesemia with secondary hypocalcemia. The failure to absorb Mg by the bowel causes diarrhea while renal magnesium losses cause hypomagnesemia.
Epidemiological data does not yet exist.
The gene is 199 kb in size. It is known as TRPM6 and CHAK2. It is located on chromosome 9 at position 9q22. It consists of 39 exons. the first exon is not translated.
Hypomagnesemia is the main symptom. It occurs in conjunction with a secondary hypocalcemia. Often the disturbance of enteral magnesium resorption leads to diarrhea. Neurologically, convulsions and tetany dominate the clinical picture. By the pathologist calcinosis is found in several organs including myocardium, kidneys, and cerebral arteries.
The translation product a protein of 2,022 amino acids (234 kD). It consists of a predicted ion channel domain and a protein kinase domain. The gene is expressed in enteral and renal epithelium cells. Obviously its function is connected to magnesium absorption.
Predominant indications for molecular diagnostic are family counseling and improvement of diagnostic precision.
Limited data exist for genotype phenotype correlation. If a mutation of this gene was detected, one would stop oral magnesium supplementation to not aggravate the gastrointestinal symptoms.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 25 days | |
Specimen type | genomic DNA |
1. |
Li M et al. (2006) Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. |
2. |
Lee N et al. (2003) Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3). |
3. |
Grimm C et al. (2003) Molecular and functional characterization of the melastatin-related cation channel TRPM3. |
4. |
Nair AV et al. (2012) Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy. |
5. |
Song Y et al. (2009) Common genetic variants of the ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7), magnesium intake, and risk of type 2 diabetes in women. |
6. |
Okumus S et al. (2013) Association transient receptor potential melastatin channel gene polymorphism with primary open angle glaucoma. |
8. |
Saraç M et al. (2016) Magnesium-permeable polymorphisms in patients with meningomyelocele. |
10. |
Fu CY et al. (2019) Increased risk of post-stroke epilepsy in Chinese patients with a TRPM6 polymorphism. |
11. |
Li M et al. (2007) Molecular determinants of Mg2+ and Ca2+ permeability and pH sensitivity in TRPM6 and TRPM7. |
12. |
Schlingmann KP et al. (2007) TRPM6 and TRPM7--Gatekeepers of human magnesium metabolism. |
13. |
Schmitz C et al. (2005) The channel kinases TRPM6 and TRPM7 are functionally nonredundant. |
14. |
NCBI article NCBI 140803 |
15. |
OMIM.ORG article Omim 607009 |
16. |
Orphanet article Orphanet ID 120301 |
17. |
Wikipedia article Wikipedia EN (TRPM6) |