Nephrotic syndrome, type 6

Summary

Nephrotic syndrome, type 6 (MONDO:0013619) is a disease caused by PTPRO (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PTPRO (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 158

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 6
Mondo ID	MONDO:0013619
OMIM	614196
DOID	DOID:0080384
UMLS	C3280100
MedGen	481730
GARD	0015770
Is cancer (heuristic)	no

Also known as: nephrotic syndrome caused by mutation in PTPRO · nephrotic syndrome, type 6 · NPHS6 · PTPRO nephrotic syndrome

Data availability: 158 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › familial idiopathic steroid-resistant nephrotic syndrome › nephrotic syndrome, type 6

Related subtypes (13): nephrotic syndrome, type 2, focal segmental glomerulosclerosis 1, nephrotic syndrome, type 3, familial steroid-resistant nephrotic syndrome with sensorineural deafness, nephrotic syndrome, type 8, nephrotic syndrome, type 9, nephrotic syndrome, type 10, nephrotic syndrome, type 11, nephrotic syndrome, type 12, nephrotic syndrome, type 13, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation, familial idiopathic steroid-resistant nephrotic syndrome with minimal changes, familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

158 retrieved; paginated sample, class counts are floors:

134 uncertain significance, 8 benign/likely benign, 7 conflicting classifications of pathogenicity, 3 likely benign, 3 likely pathogenic, 2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
30110	NM_030667.3(PTPRO):c.2627+1G>T	PTPRO	Pathogenic	no assertion criteria provided
30111	NM_030667.3(PTPRO):c.2829+1G>A	PTPRO	Pathogenic	no assertion criteria provided
3574470	NM_030667.3(PTPRO):c.1758del (p.Val587fs)	PTPRO	Likely pathogenic	criteria provided, single submitter
3574482	NM_030667.3(PTPRO):c.2027del (p.Lys676fs)	PTPRO	Likely pathogenic	criteria provided, single submitter
3574503	NM_030667.3(PTPRO):c.2712-1G>A	PTPRO	Likely pathogenic	criteria provided, single submitter
3574486	NM_030667.3(PTPRO):c.2127A>G (p.Arg709=)	LOC126861467	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1903597	NM_030667.3(PTPRO):c.2628-13T>A	PTPRO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2014947	NM_030667.3(PTPRO):c.2747+18T>G	PTPRO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2048493	NM_030667.3(PTPRO):c.1578T>C (p.Phe526=)	PTPRO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2170933	NM_030667.3(PTPRO):c.60C>G (p.Leu20=)	PTPRO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3574452	NM_030667.3(PTPRO):c.1317G>A (p.Val439=)	PTPRO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
981948	NM_030667.3(PTPRO):c.3497G>C (p.Gly1166Ala)	PTPRO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3574483	NM_030667.3(PTPRO):c.2050C>T (p.Arg684Cys)	LOC126861467	Uncertain significance	criteria provided, single submitter
3574484	NM_030667.3(PTPRO):c.2051G>A (p.Arg684His)	LOC126861467	Uncertain significance	criteria provided, single submitter
3574485	NM_030667.3(PTPRO):c.2117G>A (p.Cys706Tyr)	LOC126861467	Uncertain significance	criteria provided, single submitter
3574487	NM_030667.3(PTPRO):c.2143A>G (p.Met715Val)	LOC126861467	Uncertain significance	criteria provided, single submitter
1028900	NM_030667.3(PTPRO):c.1733C>T (p.Thr578Ile)	PTPRO	Uncertain significance	criteria provided, single submitter
1032235	NM_030667.3(PTPRO):c.1792C>G (p.Leu598Val)	PTPRO	Uncertain significance	criteria provided, single submitter
1477792	NM_030667.3(PTPRO):c.1611G>T (p.Met537Ile)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
1505962	NM_030667.3(PTPRO):c.998C>T (p.Ser333Leu)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
1516890	NM_030667.3(PTPRO):c.497T>C (p.Met166Thr)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
1517987	NM_030667.3(PTPRO):c.1085A>G (p.His362Arg)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
1939061	NM_030667.3(PTPRO):c.2473G>A (p.Val825Met)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2040872	NM_030667.3(PTPRO):c.946G>A (p.Val316Ile)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2044986	NM_030667.3(PTPRO):c.1255A>G (p.Ser419Gly)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2169865	NM_030667.3(PTPRO):c.689T>C (p.Val230Ala)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2189431	NM_030667.3(PTPRO):c.1551T>G (p.Ile517Met)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2190661	NM_030667.3(PTPRO):c.2519C>T (p.Thr840Ile)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2231271	NM_030667.3(PTPRO):c.1885A>G (p.Ile629Val)	PTPRO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435292	NM_030667.3(PTPRO):c.2750C>T (p.Pro917Leu)	PTPRO	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PTPRO	Strong	Autosomal recessive	nephrotic syndrome, type 6	4
PTPRU	Strong	Autosomal recessive	nephrotic syndrome, type 6	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPRO	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PTPRO	HGNC:9678	ENSG00000151490	Q16827	Receptor-type tyrosine-protein phosphatase O	gencc,clinvar
PTPRU	HGNC:9683	ENSG00000060656	Q92729	Receptor-type tyrosine-protein phosphatase U	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPRO	Receptor-type tyrosine-protein phosphatase O	Possesses tyrosine phosphatase activity.
PTPRU	Receptor-type tyrosine-protein phosphatase U	Tyrosine-protein phosphatase which dephosphorylates CTNNB1.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Phosphatase	2	83.9×	1e-04

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPRO	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
PTPRU	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, MAM_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
metanephric glomerulus	1
renal glomerulus	1
ectocervix	1
endocervix	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPRO	214	broad	marker	renal glomerulus, metanephric glomerulus, cortical plate
PTPRU	239	ubiquitous	marker	endocervix, olfactory segment of nasal mucosa, ectocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPRO	1,520
PTPRU	206

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPRO	Q16827	2
PTPRU	Q92729	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by NTRK3 (TRKC)	1	571.0×	0.004	PTPRO
Signaling by SCF-KIT	1	124.1×	0.008	PTPRU

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of canonical Wnt signaling pathway	2	117.8×	0.002	PTPRO, PTPRU
slit diaphragm assembly	1	4213.0×	0.002	PTPRO
negative regulation of retinal ganglion cell axon guidance	1	4213.0×	0.002	PTPRO
regulation of glomerular filtration	1	2106.5×	0.002	PTPRO
negative regulation of glomerular filtration	1	2106.5×	0.002	PTPRO
cell surface receptor protein tyrosine phosphatase signaling pathway	1	1053.2×	0.004	PTPRU
homotypic cell-cell adhesion	1	842.6×	0.004	PTPRU
podocyte differentiation	1	702.2×	0.004	PTPRO
glomerulus development	1	648.1×	0.004	PTPRO
positive regulation of cell-cell adhesion mediated by cadherin	1	648.1×	0.004	PTPRU
negative regulation of cell-substrate adhesion	1	526.6×	0.004	PTPRO
regulation of synapse organization	1	324.1×	0.006	PTPRO
animal organ regeneration	1	300.9×	0.006	PTPRU
monocyte chemotaxis	1	290.6×	0.006	PTPRO
protein localization to cell surface	1	247.8×	0.007	PTPRU
lamellipodium assembly	1	221.7×	0.007	PTPRO
response to glucocorticoid	1	162.0×	0.009	PTPRU
negative regulation of neuron projection development	1	118.7×	0.012	PTPRO
protein dephosphorylation	1	110.9×	0.012	PTPRU
cell morphogenesis	1	78.8×	0.016	PTPRO
neuron projection development	1	61.1×	0.020	PTPRU
negative regulation of cell migration	1	55.8×	0.021	PTPRU
axon guidance	1	45.3×	0.025	PTPRO
negative regulation of cell population proliferation	1	21.1×	0.051	PTPRU
cell adhesion	1	18.7×	0.055	PTPRU
signal transduction	1	8.0×	0.121	PTPRU

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTPRO	0	0
PTPRU	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PTPRO	7	Binding:7
PTPRU	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRO	3.1.3.48	protein-tyrosine-phosphatase
PTPRU	3.1.3.48	protein-tyrosine-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	PTPRO, PTPRU
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PTPRO	7	—
PTPRU	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.