Proteinuric renal disease
Gene: PODXL
Comment on list classification:
2 cases with functional evidence that the variants may cause disease. Additional case of patient with SRNS where variant is predicted to be deleterious. 1 case with a variant in an individual with FSGS but no evidence variant affects protein function.
A further case with a patient with compound heterozygous variants in PODXL and congenital nephrotic syndrome.Created: 26 Mar 2019, 5:24 p.m.
PMID: 30523047 - Lin et al 2019 - heterozygous nonsense PODXL mutations in two unrelated pedigrees: c.C976T (p. Arg326X) in a Chinese pedigree that was associated with proteinuria and renal insufficiency, and c.C1133G (p. Ser378X) in a British–Indian AD-FSGS pedigree. They also provide evidence with in vitro study showing that the heterozygous nonsense PODXL mutations may be causative in AD-FSGS.
PMID: 29244787 - Kang et al 2017 - report a patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL. The 2 variants were a missense mutation at the initiation codon c.3G>T (p.Met1Ile) and a nonsense mutation at c.1023G>A (p.Trp341Ter).
PMID: 28117080 - Bierzynska et al 2017 - Whole exome sequencing was performed on 187 paediatric patients with Steroid Resistant Nephrotic Syndrome (SRNS). 1 case found with variant in PODXL c.1427A>T:p.His476Leu which is predicted to be deleterious.
PMID: 24048372 - Barua et al 2014 - exome sequencing of affected cousins from an autosomal dominant pedigree with FSGS identified a cosegregating private variant, PODXL p.L442R. However, this change does not alter protein stability, extracellular domain glycosylation, cell surface expression, global subcellular localization, or interaction with its intracellular binding partner ezrin.Created: 26 Mar 2019, 5:19 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: PODXL; Suggested initial gene rating: green; Evidence for inclusion: PMID: 30523047; PMID: 29244787; Other comments: Two unrelated families with rare AD PODXL nonsense variants, plus functional analysis in PMID: 30523047 . Other unrelated reports of patients with PODXL and nephrotic syndrome.Created: 4 Feb 2019, 10:41 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Congenital nephrotic syndrome
Publications
Tag gene-checked tag was added to gene: PODXL.
Phenotypes for gene: PODXL were changed from to Congenital nephrotic syndrome
Publications for gene: PODXL were set to
Mode of inheritance for gene: PODXL was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: podxl has been classified as Green List (High Evidence).
gene: PODXL was added gene: PODXL was added to Proteinuric renal disease. Sources: NHS GMS Mode of inheritance for gene: PODXL was set to