Renal tubulopathies

Gene: TRPM6

Green List (high evidence)

TRPM6 (transient receptor potential cation channel subfamily M member 6)
EnsemblGeneIds (GRCh38): ENSG00000119121
EnsemblGeneIds (GRCh37): ENSG00000119121
OMIM: 607009, Gene2Phenotype
TRPM6 is in 8 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changing rating from red to green as > 3 cases reported.
Created: 5 Sep 2019, 10:28 p.m. | Last Modified: 5 Sep 2019, 10:28 p.m.
Panel Version: 1.178
Comment on list classification: Changing rating from red to green as > 3 cases reported.
Created: 5 Sep 2019, 10:27 p.m. | Last Modified: 5 Sep 2019, 10:27 p.m.
Panel Version: 1.177
Associated with Hypomagnesemia 1, intestinal #602014 in OMIM.

PMID: 12032568 - Schlingmann et al 2002 - 5 families (2 Turkish, 1 Swedish, 1 Israeli, and 1 Albanian) with hypomagnesemia with secondary hypocalcemia and mutations in the TRPM6 gene. In three families the parents were consanguineous and the affected individuals had homozygous variants. In 2 non-consanguineous families the affected children were compound heterozygous for TRPM6 mutations. The age at onset of symptoms varied from 3 weeks to 4 months. Seizures were the first symptoms detected. They also identified TRPM6 expression in kidney, and they report that the individuals studied showed inappropriately high fractional magnesium excretion rates, indicating an additional role of impaired renal magnesium reabsorption in HSH. This is confirmed by the characterisation of a considerable renal leak of magnesium in HSH patients in an accompanying report.

PubMed: 12032570 - Walder et al 2002 - identified homozygous mutations in each of six consanguineous families, and a heterozygous mutation in a nonconsanguineous family with Familial hypomagnesemia with secondary hypocalcemia. The search was narrowed to TPRM6 by homozygosity mapping and then identifying TRPM6 as a likely candidate gene. The gene was then sequenced in each of the families. 3 families were Bedouin kindreds from Israel with the same variant in a splice donor, the other families (each with different variants) were an Arab family from Greece, a family from Germany and 2 Arab families from Israel.

PMID: 23942199 - Lainez et al. 2014 - report from five new missense mutations found in five patients with HSH.
Created: 2 Sep 2019, 7:52 p.m. | Last Modified: 2 Sep 2019, 7:52 p.m.
Panel Version: 1.82
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: TRPM6; Suggested initial gene rating: green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided
Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypomagnesemia 1, intestinal, MIM 602014

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • Expert list
Phenotypes
  • Hypomagnesemia 1, intestinal, 602014
OMIM
607009
Clinvar variants
Variants in TRPM6
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

5 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: trpm6 has been classified as Green List (High Evidence).

5 Sep 2019, Gel status: 1

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: trpm6 has been classified as Red List (Low Evidence).

5 Sep 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TRPM6 were set to 12032568

18 Jun 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TRPM6 were changed from 602014 to Hypomagnesemia 1, intestinal, 602014

3 Feb 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to TRPM6.

28 Mar 2016, Gel status: 0

Created

Richard Scott (Genomics England Curator)

TRPM6 was created by richardhywel

28 Mar 2016, Gel status: 0

Added New Source

Richard Scott (Genomics England Curator)

TRPM6 was added to Renal tubular acidosispanel. Sources: Expert list