Nephrotic syndrome, type 18

Summary

Nephrotic syndrome, type 18 (MONDO:0032581) is a disease caused by NUP133 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NUP133 (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 18
Mondo ID	MONDO:0032581
OMIM	618177
DOID	DOID:0080393
UMLS	C4748549
MedGen	1648464
GARD	0016300
Is cancer (heuristic)	no

Also known as: NPHS18

Data availability: 10 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 18

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 17, 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

10 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333537	NM_018230.3(NUP133):c.196C>T (p.Arg66Ter)	NUP133	Likely pathogenic	criteria provided, single submitter
590319	NM_018230.3(NUP133):c.691C>G (p.Arg231Gly)	NUP133	Likely pathogenic	criteria provided, multiple submitters, no conflicts
590321	NM_018230.3(NUP133):c.2922T>G (p.Ser974Arg)	NUP133	Likely pathogenic	criteria provided, single submitter
590320	NM_018230.3(NUP133):c.3164T>C (p.Leu1055Ser)	NUP133	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029680	NM_018230.3(NUP133):c.2089G>A (p.Asp697Asn)	NUP133	Uncertain significance	criteria provided, single submitter
1029681	NM_018230.3(NUP133):c.3299T>C (p.Ile1100Thr)	NUP133	Uncertain significance	criteria provided, single submitter
1333502	NM_018230.3(NUP133):c.3095T>C (p.Ile1032Thr)	NUP133	Uncertain significance	criteria provided, single submitter
1414917	NM_018230.3(NUP133):c.3359C>T (p.Pro1120Leu)	NUP133	Uncertain significance	criteria provided, multiple submitters, no conflicts
977446	NM_018230.3(NUP133):c.1216C>T (p.Gln406Ter)	NUP133	Uncertain significance	criteria provided, single submitter
1327014	NM_018230.3(NUP133):c.1263C>T (p.Asn421=)	NUP133	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
NUP133	Strong	Autosomal recessive	nephrotic syndrome, type 18	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP133	Orphanet:2065	Galloway-Mowat syndrome
NUP133	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
NUP133	HGNC:18016	ENSG00000069248	Q8WUM0	Nuclear pore complex protein Nup133	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP133	Nuclear pore complex protein Nup133	Involved in poly(A)+ RNA transport.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUP133	Scaffold/PPI	no		Nucleoporin_Nup133/Nup155_C, WD40/YVTN_repeat-like_dom_sf, Nup133-like

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
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP133	297	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP133	3,453

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP133	Q8WUM0	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. 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
Postmitotic nuclear pore complex (NPC) reformation	1	407.9×	0.007	NUP133
IPs transport between nucleus and cytosol	1	380.7×	0.007	NUP133
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.007	NUP133
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.007	NUP133
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.007	NUP133
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.007	NUP133
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.007	NUP133
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.007	NUP133
Nuclear import of Rev protein	1	335.9×	0.007	NUP133
Vpr-mediated nuclear import of PICs	1	335.9×	0.007	NUP133
Transport of the SLBP independent Mature mRNA	1	326.3×	0.007	NUP133
SUMOylation of SUMOylation proteins	1	326.3×	0.007	NUP133
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.007	NUP133
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.007	NUP133
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.007	NUP133
SUMOylation of ubiquitinylation proteins	1	292.8×	0.007	NUP133
NS1 Mediated Effects on Host Pathways	1	285.5×	0.007	NUP133
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.007	NUP133
Viral Messenger RNA Synthesis	1	259.6×	0.007	NUP133
SUMOylation of DNA replication proteins	1	248.3×	0.007	NUP133
SUMOylation of RNA binding proteins	1	237.9×	0.007	NUP133
snRNP Assembly	1	211.5×	0.008	NUP133
tRNA processing in the nucleus	1	196.9×	0.008	NUP133
SUMOylation of chromatin organization proteins	1	158.6×	0.009	NUP133
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.009	NUP133
ISG15 antiviral mechanism	1	150.3×	0.009	NUP133
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.009	NUP133
Regulation of HSF1-mediated heat shock response	1	139.3×	0.009	NUP133
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.011	NUP133
HCMV Late Events	1	98.5×	0.013	NUP133

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
transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery	1	4213.0×	0.002	NUP133
nuclear pore organization	1	2106.5×	0.002	NUP133
nephron development	1	1872.4×	0.002	NUP133
paraxial mesoderm development	1	1685.2×	0.002	NUP133
somite development	1	1123.5×	0.002	NUP133
poly(A)+ mRNA export from nucleus	1	674.1×	0.003	NUP133
neural tube development	1	526.6×	0.003	NUP133
nucleocytoplasmic transport	1	391.9×	0.004	NUP133
mRNA export from nucleus	1	295.6×	0.004	NUP133
neurogenesis	1	208.1×	0.005	NUP133
protein import into nucleus	1	144.0×	0.007	NUP133

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
NUP133	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	NUP133

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)
NUP133	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.