Nephrotic syndrome, type 17

Summary

Nephrotic syndrome, type 17 (MONDO:0032580) is a disease caused by NUP85 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: NUP85 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 17
Mondo ID	MONDO:0032580
OMIM	618176
DOID	DOID:0080392
UMLS	C4748545
MedGen	1648294
GARD	0016299
Is cancer (heuristic)	no

Also known as: NPHS17

Data availability: 11 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 › nephrotic syndrome, type 17

Related subtypes (17): congenital nephrotic syndrome, Finnish type, nephrotic syndrome, type 4, LAMB2-related infantile-onset nephrotic syndrome, immunoglobulin-mediated membranoproliferative glomerulonephritis, familial idiopathic steroid-resistant nephrotic syndrome, nephrotic syndrome, type 20, nephrotic syndrome, type 22, nephrotic syndrome, type 23, nephrotic syndrome, type 24, nephrotic syndrome, IIa 26, nephrotic syndrome, type 18, nephrotic syndrome, type 19, nephrotic syndrome, type 21, nephrotic syndrome 14, nephrotic syndrome 15, nephrotic syndrome 16, idiopathic multidrug-resistant nephrotic syndrome

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

11 retrieved; paginated sample, class counts are floors:

4 benign, 3 uncertain significance, 3 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
590317	NM_024844.5(NUP85):c.405+1G>A	NUP85	Pathogenic	no assertion criteria provided
590316	NM_024844.5(NUP85):c.1933C>T (p.Arg645Trp)	GGA3	Likely pathogenic	criteria provided, single submitter
590318	NM_024844.5(NUP85):c.1741G>C (p.Ala581Pro)	GGA3	Likely pathogenic	criteria provided, single submitter
3769651	NM_024844.5(NUP85):c.1379G>A (p.Arg460Gln)	NUP85	Likely pathogenic	criteria provided, single submitter
1030881	NM_024844.5(NUP85):c.1465T>C (p.Trp489Arg)	GGA3	Uncertain significance	criteria provided, single submitter
3780052	NM_024844.5(NUP85):c.1680_1682del (p.Leu561del)	NUP85	Uncertain significance	criteria provided, single submitter
590315	NM_024844.5(NUP85):c.1430C>T (p.Ala477Val)	NUP85	Uncertain significance	criteria provided, single submitter
1327037	NM_024844.5(NUP85):c.361+25C>T	NUP85	Benign	criteria provided, multiple submitters, no conflicts
1327039	NM_024844.5(NUP85):c.735C>T (p.Pro245=)	NUP85	Benign	criteria provided, multiple submitters, no conflicts
1327040	NM_024844.5(NUP85):c.1396+27T>C	NUP85	Benign	criteria provided, multiple submitters, no conflicts
1327041	NM_024844.5(NUP85):c.1740C>T (p.Asp580=)	NUP85	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
NUP85	Strong	Autosomal recessive	nephrotic syndrome, type 17	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP85	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
NUP85	Orphanet:808	Seckel 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
NUP85	HGNC:8734	ENSG00000125450	Q9BW27	Nuclear pore complex protein Nup85	gencc,clinvar
GGA3	HGNC:17079	ENSG00000125447	Q9NZ52	ADP-ribosylation factor-binding protein GGA3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP85	Nuclear pore complex protein Nup85	Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance.
GGA3	ADP-ribosylation factor-binding protein GGA3	Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUP85	Other/Unknown	no		Nucleoporin_Nup85
GGA3	Antibody/Immunoglobulin	yes		VHS_dom, GAT_dom, Clathrin_a/b/g-adaptin_app_Ig

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
granulocyte	1
pylorus	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP85	258	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
GGA3	268	ubiquitous	marker	sural nerve, granulocyte, pylorus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP85	2,757
GGA3	2,174

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GGA3	Q9NZ52	6
NUP85	Q9BW27	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. 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
MET receptor recycling	1	571.0×	0.015	GGA3
Postmitotic nuclear pore complex (NPC) reformation	1	203.9×	0.015	NUP85
IPs transport between nucleus and cytosol	1	190.3×	0.015	NUP85
IP3 and IP4 transport between cytosol and nucleus	1	190.3×	0.015	NUP85
IP6 and IP7 transport between cytosol and nucleus	1	190.3×	0.015	NUP85
Transport of Ribonucleoproteins into the Host Nucleus	1	178.4×	0.015	NUP85
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	178.4×	0.015	NUP85
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	178.4×	0.015	NUP85
NEP/NS2 Interacts with the Cellular Export Machinery	1	173.0×	0.015	NUP85
Nuclear import of Rev protein	1	167.9×	0.015	NUP85
Vpr-mediated nuclear import of PICs	1	167.9×	0.015	NUP85
Transport of the SLBP independent Mature mRNA	1	163.1×	0.015	NUP85
SUMOylation of SUMOylation proteins	1	163.1×	0.015	NUP85
Transport of the SLBP Dependant Mature mRNA	1	158.6×	0.015	NUP85
Rev-mediated nuclear export of HIV RNA	1	158.6×	0.015	NUP85
Nuclear Pore Complex (NPC) Disassembly	1	154.3×	0.015	NUP85
SUMOylation of ubiquitinylation proteins	1	146.4×	0.015	NUP85
NS1 Mediated Effects on Host Pathways	1	142.8×	0.015	NUP85
Transport of Mature mRNA Derived from an Intronless Transcript	1	135.9×	0.015	NUP85
Viral Messenger RNA Synthesis	1	129.8×	0.015	NUP85
TBC/RABGAPs	1	129.8×	0.015	GGA3
SUMOylation of DNA replication proteins	1	124.1×	0.015	NUP85
SUMOylation of RNA binding proteins	1	119.0×	0.015	NUP85
snRNP Assembly	1	105.7×	0.016	NUP85
tRNA processing in the nucleus	1	98.5×	0.016	NUP85
SUMOylation of chromatin organization proteins	1	79.3×	0.019	NUP85
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	76.1×	0.019	NUP85
ISG15 antiviral mechanism	1	75.1×	0.019	NUP85
SUMOylation of DNA damage response and repair proteins	1	73.2×	0.019	NUP85
Regulation of HSF1-mediated heat shock response	1	69.6×	0.019	NUP85

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
positive regulation of lysosomal protein catabolic process	1	1685.2×	0.009	GGA3
nephron development	1	936.2×	0.009	NUP85
macrophage chemotaxis	1	468.1×	0.009	NUP85
negative regulation of amyloid-beta formation	1	443.5×	0.009	GGA3
protein targeting to lysosome	1	312.1×	0.009	GGA3
Golgi to plasma membrane transport	1	280.9×	0.009	GGA3
Golgi to plasma membrane protein transport	1	263.3×	0.009	GGA3
protein localization to cell surface	1	247.8×	0.009	GGA3
lamellipodium assembly	1	221.7×	0.009	NUP85
nucleocytoplasmic transport	1	195.9×	0.009	NUP85
mRNA export from nucleus	1	147.8×	0.010	NUP85
protein destabilization	1	145.3×	0.010	GGA3
endocytic recycling	1	133.8×	0.010	GGA3
protein catabolic process	1	118.7×	0.011	GGA3
protein import into nucleus	1	72.0×	0.017	NUP85
regulation of protein stability	1	62.9×	0.018	GGA3
intracellular protein transport	1	32.4×	0.032	GGA3
positive regulation of DNA-templated transcription	1	14.0×	0.070	NUP85

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
NUP85	0	0
GGA3	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	1	GGA3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NUP85

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)
NUP85	0	—
GGA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.