Proteinuric renal disease
Gene: TNS2
Comment on list classification: Rating green as there are 4 unrelated families (plus another with possible founder mutation in common with one of the 4) with variants in this gene and a relevant phenotype.Created: 1 Apr 2019, 9:50 p.m.
No association with any phenotype in OMIM or Gene2Phenotype.
PMID : 29773874 - Ashraf et al 2018 - homozygosity mapping combined with whole exome sequencing in multiple families with Nephrotic syndrome. TNS2 variants found in 5 families (1 Turkish, 1 European, 1 Nigerian, 2 Indian). 3 families showed homozygous variants, 2 compound heterozygous. One Indian family was homozygous for a c.2574C>G, p.Ile858Met variant. The other Indian family was compound heterozygous for this variant and another c.1693C>T, p.Arg565Trp suggesting that the c.2574C>G variant may be a founder allele. Altered amino acid residues were well conserved throughout evolution. Both TNS2 and DLC1 colocalize with an antibody labeling phosphotyrosine at focal and fibrillar adhesions, consistent with the role of focal adhesions in podocyte migration and the pathogenesis of NS. TNS2 had been shown to interact with DLC1, so the authors performed coIP upon co-overexpression in HEK293T cells and confirmed TNS2-DLC1 interaction, however, none of the TNS2 or DLC1 missense mutations identified in NS patients abrogated this interaction. Discussed this with the Genomics England Rare Disease clinical team and we decided that TNS2 variants may be acting in a different way other than interacting with DLC1, so ok to rate green.Created: 1 Apr 2019, 9:42 p.m.
This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: TNS2; Suggested initial gene rating: green; Evidence for inclusion: PMID : 29773874; Other comments: Four unrelated families with rare AR variants in TNS2Created: 4 Feb 2019, 10:41 a.m.
Publications
Tag gene-checked tag was added to gene: TNS2.
Phenotypes for gene: TNS2 were changed from to nephrotic syndrome
Publications for gene: TNS2 were set to
Mode of inheritance for gene: TNS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: tns2 has been classified as Green List (High Evidence).
gene: TNS2 was added gene: TNS2 was added to Proteinuric renal disease. Sources: NHS GMS Mode of inheritance for gene: TNS2 was set to