Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
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Channel kinase 2

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.

Epidemiology

Epidemiological data does not yet exist.

Gene Structure

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.

Phenotype

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.

Pathology

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.

Test Strategy

Predominant indications for molecular diagnostic are family counseling and improvement of diagnostic precision.

Interpretation

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.

Genetests:

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

Related Diseases:

Intestinal hypomagnesemia with secondary hypocalcemia
TRPM6

References:

1.

Schmitz C et al. (2005) The channel kinases TRPM6 and TRPM7 are functionally nonredundant.

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2.

Li M et al. (2006) Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7.

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3.

Schlingmann KP et al. (2007) TRPM6 and TRPM7--Gatekeepers of human magnesium metabolism.

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4.

Li M et al. (2007) Molecular determinants of Mg2+ and Ca2+ permeability and pH sensitivity in TRPM6 and TRPM7.

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5.

Nair AV et al. (2012) Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy.

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6.

Grimm C et al. (2003) Molecular and functional characterization of the melastatin-related cation channel TRPM3.

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7.

Lee N et al. (2003) Expression and characterization of human transient receptor potential melastatin 3 (hTRPM3).

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8.

NCBI article

NCBI 140803 external link
9.

OMIM.ORG article

Omim 607009 external link
10.

Orphanet article

Orphanet ID 120301 external link
11.

Wikipedia article

Wikipedia EN (TRPM6) external link
Update: Aug. 14, 2020
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