Nephrotic syndrome, type 8

Summary

Nephrotic syndrome, type 8 (MONDO:0014099) is a disease caused by ARHGDIA (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ARHGDIA (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 8
Mondo ID	MONDO:0014099
OMIM	615244
DOID	DOID:0080389
UMLS	C3808953
MedGen	815283
GARD	0015925
Is cancer (heuristic)	no

Also known as: ARHGDIA nephrotic syndrome · nephrotic syndrome caused by mutation in ARHGDIA · nephrotic syndrome, type 8 · NPHS8

Data availability: 10 ClinVar variants · 4 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 8

Related subtypes (13): nephrotic syndrome, type 2, focal segmental glomerulosclerosis 1, nephrotic syndrome, type 3, nephrotic syndrome, type 6, familial steroid-resistant nephrotic syndrome with sensorineural deafness, 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

10 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
140593	NM_004309.6(ARHGDIA):c.518G>T (p.Gly173Val)	ARHGDIA	Pathogenic	no assertion criteria provided
140594	NM_004309.6(ARHGDIA):c.358C>T (p.Arg120Ter)	ARHGDIA	Pathogenic	no assertion criteria provided
3769217	NC_000017.10:g.(?79825596)(79828874_?)del	ARHGDIA	Pathogenic	criteria provided, single submitter
50501	NM_004309.6(ARHGDIA):c.547GAC[2] (p.Asp185del)	ARHGDIA	Pathogenic	no assertion criteria provided
3064694	NM_004309.6(ARHGDIA):c.*167dup	ARHGDIA	Likely pathogenic	criteria provided, single submitter
1030365	NM_004309.6(ARHGDIA):c.275-20G>T	ARHGDIA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030364	NM_004309.6(ARHGDIA):c.*41A>G	ARHGDIA	Uncertain significance	criteria provided, single submitter
1177422	NM_004309.6(ARHGDIA):c.151T>C (p.Tyr51His)	ARHGDIA	Uncertain significance	criteria provided, single submitter
915863	NM_004309.6(ARHGDIA):c.*243G>A	ARHGDIA	Uncertain significance	criteria provided, multiple submitters, no conflicts
3338251	NM_004309.6(ARHGDIA):c.*362G>T	ARHGDIA	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
ARHGDIA	Strong	Autosomal recessive	nephrotic syndrome, type 8	5

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARHGDIA	HGNC:678	ENSG00000141522	P52565	Rho GDP-dissociation inhibitor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARHGDIA	Rho GDP-dissociation inhibitor 1	Controls Rho proteins homeostasis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARHGDIA	Other/Unknown	no		Rho_GDI, Ig_E-set, RhoGDI_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
granulocyte	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARHGDIA	292	ubiquitous	marker	granulocyte, colonic epithelium, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARHGDIA	2,778

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARHGDIA	P52565	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 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
Axonal growth stimulation	1	2855.0×	0.003	ARHGDIA
Axonal growth inhibition (RHOA activation)	1	1268.9×	0.004	ARHGDIA
RHOH GTPase cycle	1	308.6×	0.010	ARHGDIA
RHOG GTPase cycle	1	148.3×	0.012	ARHGDIA
RHOC GTPase cycle	1	146.4×	0.012	ARHGDIA
RAC2 GTPase cycle	1	126.9×	0.012	ARHGDIA
RHOA GTPase cycle	1	74.6×	0.016	ARHGDIA
CDC42 GTPase cycle	1	72.3×	0.016	ARHGDIA
RAC1 GTPase cycle	1	61.1×	0.016	ARHGDIA

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of synaptic vesicle cycle	1	1123.5×	0.005	ARHGDIA
regulation of Rho protein signal transduction	1	510.7×	0.005	ARHGDIA
semaphorin-plexin signaling pathway	1	401.2×	0.005	ARHGDIA
Rho protein signal transduction	1	247.8×	0.006	ARHGDIA
regulation of protein localization	1	205.5×	0.006	ARHGDIA
negative regulation of apoptotic process	1	34.8×	0.029	ARHGDIA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
ARHGDIA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ARHGDIA	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	ARHGDIA

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARHGDIA	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.