Proteinuric renal disease
Gene: TPRKBComment on list classification: Changed rating to Amber to reflect NHS signed-off rating, will be examined at next panel review.Created: 16 Oct 2020, 8:06 a.m. | Last Modified: 16 Oct 2020, 8:06 a.m.
Panel Version: 2.32
2 unrelated patients with Galloway-Mowat syndrome and nephrotic syndrome with proteinuria, and homozygous missense mutations in the TPRKB gene, with functional evidence. 3rd family reported with 3 affected sibs and novel homozygous TP53RK mutation, but no functional evidence.Created: 9 Jan 2020, 3:59 a.m. | Last Modified: 9 Jan 2020, 3:59 a.m.
Panel Version: 2.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Galloway-Mowat syndrome 5, OMIM #617731
Publications
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 7 Mar 2022, 11:37 p.m. | Last Modified: 7 Mar 2022, 11:37 p.m.
Panel Version: 2.66
Comment on list classification: Changing rating from red to green, as there are 3 reported cases.Created: 21 Mar 2020, 2:39 p.m. | Last Modified: 21 Mar 2020, 2:39 p.m.
Panel Version: 2.13
TPRKB is associated with Galloway-Mowat syndrome 5 #617731 (AR) in OMIM.
PMID: 28805828 - Braun et al 2017 - screened the coding regions of OSGEP, TP53RK, TPRKB and LAGE3 in 907 individuals with early-onset nephrotic syndrome including 91 individuals with GAMOS. Identified 2 biallelic missense variants in TPRKB in 2 families with GAMOS (c.407T>C, p.Leu136Pro and c.446A>6, p.Tyr149Cys). Both sets of parents were heterozgous for the variant. Mouse embryos with knockout of Lage3, Osgep, or Tprkb reproduced the human microcephaly phenotype. No renal phenotype was observed in knockout mice or fish but they hypothesize that this is due to early lethality masking renal involvement that might occur in older animals. Functional studies also showed that knockout of these genes affect cell proliferation.
PMID: 30053862 - Hyun et al 2018 - WES on a family with three GAMOS affected siblings found a homozygous missense mutation (NM_033550, c.194A > T, p.Lys65Met) in 2 siblings (3rd not tested). Parents and an unaffected sibling were heterzygous for the variant. All three patients manifested similar phenotypes, including very early-onset nephrotic syndrome, microcephaly, dysmorphic faces, and early fatality. Renal biopsy performed on one patient revealed focal segmental glomerulosclerosis with severe tubulo-interstitial changes.
Summary: 3 familial cases. Some functional data.Created: 30 Jan 2020, 12:50 p.m. | Last Modified: 30 Jan 2020, 12:50 p.m.
Panel Version: 2.0
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: TPRKB; Suggested initial gene rating: amber; Evidence for inclusion: PMID: 28805828; Other comments: Amber: Two unrelated families with rare AR variantsCreated: 4 Feb 2019, 10:41 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Galloway-Mowat syndrome 5 #617731
Publications
Phenotypes for gene: TPRKB were changed from Galloway-Mowat syndrome 5 #617731 to Galloway-Mowat syndrome 5, OMIM:617731
Tag for-review was removed from gene: TPRKB.
Source Expert Review Green was added to TPRKB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: tprkb has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: TPRKB.
Gene: tprkb has been classified as Green List (High Evidence).
Mode of inheritance for gene: TPRKB was changed from to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPRKB were set to 28805828
Phenotypes for gene: TPRKB were changed from to Galloway-Mowat syndrome 5 #617731
Publications for gene: TPRKB were set to
gene: TPRKB was added gene: TPRKB was added to Proteinuric renal disease. Sources: NHS GMS Mode of inheritance for gene: TPRKB was set to