Proteinuric renal disease

Gene: PTPRO

I don't know

PTPRO is associated with Nephrotic syndrome, type 6 #614196 (AR) in OMIM (accessed 08/2026)

Thakor et al., 2021 (PMID 34546508) screened seven podocyte/nephrotic-syndrome-associated genes (TRPC6, WT1, LMX1B, APOL1, PTPRO, PMM2, LAMB2) in 90 Indian patients with steroid-sensitive (SSNS) and steroid-resistant (SRNS) nephrotic syndrome. They identified two likely pathogenic PTPRO variants (c.1778T>C p.(Val593Ala) and c.*16A>G) in SNSS patients. Methodology states classification was via ACMG standards, though the assertion criteria are not provided, and no clinvar nor LOVD record for either variant could be found. Supplemental table 2 suggests both variants were found in the heterozygous state, at odds with the proposed autosomal recessive inheritance mechanism in the primary case report by Ozaltin et al., 2011 (PMID 21722858).

Wharram et al., 2000 (PMID 11086029): Ptpro-/- mice show altered podocyte structure, consistent with human disease subjects- foot processes are shorter, broader and distribution of the cytoskeletal protein vimentin is altered, confirmed by electron microscopy. These structural changes were accompanied by reduced glomerular nephrin content and a measurable reduction in glomerular filtration rate, along with a predisposition to hypertension after nephrectomy. Notably, baseline Ptpro-/- mice did not show increased albuminuria under normal conditions, indicating GLEPP1 (encoded by Ptpro) loss alone produces subclinical structural podocyte anomalies and might reduce renal functional reserve.

An amber rating with watchlist designation is appropriate, given 2 unrelated families with segregation, plus an animal model partially recapitulating the phenotype seen in humans disease subjects.

Created: 17 Aug 2026, 2:48 p.m. | Last Modified: 19 Aug 2026, 11:16 a.m.

Panel Version: 6.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 6, OMIM:614196

Publications

• 34546508
• 21722858

I don't know

Two unrelated families, Amber on our panel.

Created: 9 Jan 2020, 3:52 a.m. | Last Modified: 9 Jan 2020, 3:52 a.m.

Panel Version: 2.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 6 #614196

Publications

• 21722858
• 30065916

I don't know

Comment on list classification: Changing rating from red to amber. 2 families reported.

Created: 21 Mar 2020, 2:30 p.m. | Last Modified: 21 Mar 2020, 2:30 p.m.

Panel Version: 2.10

Associated with Nephrotic syndrome, type 6 #614196 (AR) in OMIM.

2 families:

PMID: 21722858 - Ozaltin et al 2011 - 2 Turkish families reported, total of 5 individuals. A region of homozygosity was identified in a consangiuneous family with Idiopathic nephrotic syndrome. By direct sequencing of PTPRO a homozygous c.2627+1G>T donor splice-site mutation was identified. In a second family, a c.2745+1G>A donor splice-site mutation in PTPRO was identified. Electron microscopy identified ultrastructural alterations in podocytes in both families.

PMID: 30065916 - Trautmann et al 2018 - PodoNet Registry paper - describes the same families as Ozaltin et al.

Created: 30 Jan 2020, 2:24 p.m. | Last Modified: 30 Jan 2020, 2:24 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: PTPRO; Suggested initial gene rating: amber; Evidence for inclusion: PMID: 21722858; PMID: 30065916 ; Other comments: Amber: 5 patients from two unrelated families detected in PODONET study

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 6 #614196

Publications

• PMID: 21722858
• PMID: 30065916

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Only 2 families reported so far. Add to panel if more found.

Created: 27 May 2016, 12:47 p.m.

Green List (high evidence)

Currently on UK diagnostic panel, 2 VUS, but no positive cases over 300 tested. Listed in several reviews

Created: 19 Oct 2015, 3:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Childhood-Onset Nephrotic Syndrome

Publications

• The American Journal of Human Genetics 89, 139–147, July 15, 2011

Variants in this GENE are reported as part of current diagnostic practice