Tubulointerstitial kidney diseaseGene: GATM
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: 12 Feb 2019, 2:18 p.m.
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: 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;Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided
Created: 2 Feb 2019, 12:48 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal fanconi syndrome and kidney failure
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Publications for gene: GATM were set to
gene: GATM was added gene: GATM was added to Tubulointerstitial kidney disease. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: GATM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: GATM were set to Renal fanconi syndrome and kidney failure Mode of pathogenicity for gene: GATM was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments