Idiopathic nephrotic syndrome

Summary

Idiopathic nephrotic syndrome (MONDO:0018170) is a disease (an umbrella term covering 5 Mondo subtypes) with 2 cohort genes and 14 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous and valproic acid.

At a glance

• Prevalence: Unknown (Europe)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 9
• Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic nephrotic syndrome
Mondo ID	MONDO:0018170
Orphanet	357502
NCIT	C122796
UMLS	C3496337
MedGen	501252
GARD	0021539
Is cancer (heuristic)	no

Data availability: 9 ClinVar variants · 12 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › idiopathic nephrotic syndrome

Related subtypes (3): familial nephrotic syndrome, nephrotic syndrome ocular anomalies, steroid-resistant nephrotic syndrome

Subtypes (5): familial idiopathic steroid-resistant nephrotic syndrome, idiopathic steroid-sensitive nephrotic syndrome, sporadic idiopathic steroid-resistant nephrotic syndrome, idiopathic multidrug-resistant nephrotic syndrome, idiopathic steroid-resistant nephrotic syndrome with sensitivity to second-line immunosuppressive therapy

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

9 retrieved; paginated sample, class counts are floors:

6 pathogenic/likely pathogenic, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
370718	NM_014625.4(NPHS2):c.890C>T (p.Ala297Val)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371673	NM_014625.4(NPHS2):c.964C>T (p.Arg322Ter)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1439693	NM_014625.4(NPHS2):c.506T>C (p.Leu169Pro)	NPHS2	Pathogenic	criteria provided, multiple submitters, no conflicts
1491797	NM_014625.4(NPHS2):c.928G>A (p.Glu310Lys)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
504890	NM_014625.4(NPHS2):c.535-1G>T	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5361	NM_014625.4(NPHS2):c.412C>T (p.Arg138Ter)	NPHS2	Pathogenic	criteria provided, multiple submitters, no conflicts
562398	NM_014625.4(NPHS2):c.851C>T (p.Ala284Val)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
972638	NM_014625.4(NPHS2):c.714G>C (p.Arg238Ser)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3375428	NM_014625.4(NPHS2):c.637G>A (p.Ala213Thr)	NPHS2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NPHS2	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
NPHS2	HGNC:13394	ENSG00000116218	Q9NP85	Podocin	clinvar
AXDND1	HGNC:26564	ENSG00000162779	Q5T1B0	Axonemal dynein light chain domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NPHS2	Podocin	Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton.
AXDND1	Axonemal dynein light chain domain-containing protein 1	May be essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping and sperm flagellum assembly.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NPHS2	Other/Unknown	no		Band_7, Stomatin_HflK_fam, Band_7/stomatin-like_CS
AXDND1	Other/Unknown	no		Axonemal_dynein_light_chain, Axonemal_dynein_LC_domain

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
kidney epithelium	1
metanephric glomerulus	1
renal glomerulus	1
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NPHS2	47	tissue_specific	marker	renal glomerulus, metanephric glomerulus, kidney epithelium
AXDND1	161	tissue_specific	marker	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NPHS2	1,811
AXDND1	263

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NPHS2	Q9NP85	75.00
AXDND1	Q5T1B0	70.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nephrin family interactions	1	475.8×	0.002	NPHS2

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
metanephric podocyte development	1	4213.0×	0.001	NPHS2
manchette assembly	1	648.1×	0.004	AXDND1
glomerular filtration	1	468.1×	0.004	NPHS2
gene expression	1	39.9×	0.030	NPHS2
actin cytoskeleton organization	1	39.6×	0.030	NPHS2
spermatogenesis	1	17.6×	0.056	AXDND1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NPHS2	0	0
AXDND1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	NPHS2, AXDND1

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)
NPHS2	0	—
AXDND1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE3	3
PHASE4	2
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07151456	PHASE4	NOT_YET_RECRUITING	Short-term gluCOCOrticoid in Adult STEROID-sensitive Nephrotic Syndrome: The COCO-ASTEROID Study
NCT01346007	PHASE4	UNKNOWN	Study of 7-valent Pneumococcal Conjugate Vaccine in Children With Idiopathic Nephrotic Syndrome
NCT01092962	PHASE3	COMPLETED	Cyclophosphamide Versus Mycophenolate Mofetil for the Treatment of Steroid-dependent Nephrotic Syndrome in Children
NCT02896270	PHASE2/PHASE3	UNKNOWN	Valproic Acid for Idiopathic Nephrotic Syndrome
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT04494438	PHASE3	COMPLETED	Rituximab for Idiopathic Nephrotic Syndrome
NCT04034316	PHASE2	COMPLETED	Reduce Immunosuppression With Atmp in NS ChildrEn
NCT03949972	Not specified	RECRUITING	The FOrMe Registry (The German Focal Segmental Glomerulosclerosis and Minimal Change Disease Registry)
NCT04207580	Not specified	RECRUITING	A National Prospective Cohort of Patients With Idiopathic Nephrotic Syndrome Beginning in Childhood.
NCT06820866	Not specified	RECRUITING	Non-invasive Diagnosis of Idiopathic Nephrotic Syndromes
NCT00255398	Not specified	COMPLETED	Kidney Disease Biomarkers
NCT01609426	Not specified	COMPLETED	Factors of Steroid Dependency in Idiopathic Nephrotic Syndrome
NCT04075656	Not specified	COMPLETED	UrApp for Childhood Nephrotic Syndrome Management (Incident Cohort)
NCT04169776	Not specified	COMPLETED	Effect of Daily Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Proteinuria in Pediatric Patients With Idiopathic Nephrotic Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	1
VALPROIC ACID	4	1