Renal tubulopathies

Gene: GATM

Green List (high evidence)

GATM (glycine amidinotransferase)
EnsemblGeneIds (GRCh38): ENSG00000171766
EnsemblGeneIds (GRCh37): ENSG00000171766
OMIM: 602360, Gene2Phenotype
GATM is in 13 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changing rating from red to green as more than 3 cases reported.
Created: 4 Sep 2019, 9:38 p.m. | Last Modified: 4 Sep 2019, 9:38 p.m.
Panel Version: 1.119
Comment on mode of pathogenicity: All missense variants reported to date. In silico analysis suggests that the variants result in an additional interaction interface
Created: 4 Sep 2019, 9:38 p.m. | Last Modified: 4 Sep 2019, 9:38 p.m.
Panel Version: 1.118
PMID: 29654216 (Reichold et al 2018) reports 5 families with with a novel form of autosomal dominant kidney disease characterized by renal tubular Fanconi syndrome early in life followed by progression to renal glomerular failure in mid-adulthood. All patients show monoallelic mutations in the gene GATM. 4 heterozygous missense mutations of evolutionary conserved amino acid residues in GATM were found (c.958C>T, p.P320S; c.1006A>G, p.T336A; c.1007C>T, p.T336I; c.1022C>T, p.P341L). In each family, one variant segregated with the disorder and was fully penetrant. In silico analysis showed that the particular GATM mutations create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells.
Created: 30 Aug 2019, 3:40 p.m. | Last Modified: 4 Sep 2019, 9:35 p.m.
Panel Version: 1.116
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: GATM; Suggested initial gene rating: green; Evidence for inclusion: Reichold et al 2018 J Am Soc Nephrol 29(7): 1849-1858. PMID: 29654216Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided; Other Comments: AR LoF mutations result in cerebral creatine deficiency syndrome. AD missense mutations in critical protein region lead to creation of an additional interaction surface and protein aggregates
Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Renal fanconi syndrome and kidney failure (no MIM number); Cerebral creatine deficiency syndrome 3, MIM 612718 (AR)

Publications

  • Reichold et al 2018 J Am Soc Nephrol 29(7): 1849-1858. PMID: 29654216

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Renal fanconi syndrome and kidney failure (no MIM number)
  • Cerebral creatine deficiency syndrome 3, 612718 (AR)
OMIM
602360
Clinvar variants
Variants in GATM
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

9 Oct 2019, Gel status: 3

Set mode of pathogenicity

Eleanor Williams (Genomics England Curator)

Mode of pathogenicity for gene: GATM was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

4 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

4 Sep 2019, Gel status: 1

Set mode of pathogenicity

Eleanor Williams (Genomics England Curator)

Mode of pathogenicity for gene: GATM was changed from to None

4 Sep 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: GATM was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

18 Jun 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: GATM were changed from to Renal fanconi syndrome and kidney failure (no MIM number); Cerebral creatine deficiency syndrome 3, 612718 (AR)

18 Jun 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: GATM were set to

3 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: GATM was added gene: GATM was added to Renal tubulopathies. Sources: NHS GMS Mode of inheritance for gene: GATM was set to