Nephrotic syndrome, type 10

Summary

Nephrotic syndrome, type 10 (MONDO:0014373) is a disease caused by EMP2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EMP2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 10
Mondo ID	MONDO:0014373
OMIM	615861
DOID	DOID:0080386
UMLS	C4014507
MedGen	862944
GARD	0024991
Is cancer (heuristic)	no

Also known as: EMP2 nephrotic syndrome · nephrotic syndrome caused by mutation in EMP2 · nephrotic syndrome, type 10 · NPHS10

Data availability: 9 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 10

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 8, nephrotic syndrome, type 9, 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

9 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 2 likely pathogenic, 1 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
139532	NM_001424.6(EMP2):c.21C>G (p.Phe7Leu)	EMP2	Pathogenic	no assertion criteria provided
3237408	NM_001424.6(EMP2):c.78+1G>C	EMP2	Likely pathogenic	criteria provided, single submitter
3600404	NM_001424.6(EMP2):c.87_89del (p.Trp29_Val30delinsTer)	EMP2	Likely pathogenic	criteria provided, single submitter
1312429	NM_001424.6(EMP2):c.497G>A (p.Arg166His)	EMP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
139531	NM_001424.6(EMP2):c.184C>T (p.Gln62Ter)	EMP2	Uncertain significance	criteria provided, single submitter
139533	NM_001424.6(EMP2):c.28G>A (p.Ala10Thr)	EMP2	Uncertain significance	criteria provided, single submitter
2038102	NM_001424.6(EMP2):c.188C>T (p.Ala63Val)	EMP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2180054	NM_001424.6(EMP2):c.427T>C (p.Tyr143His)	EMP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
258093	NM_001424.6(EMP2):c.170-14C>T	EMP2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
EMP2	Strong	Autosomal recessive	nephrotic syndrome, type 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EMP2	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
EMP2	HGNC:3334	ENSG00000213853	P54851	Epithelial membrane protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EMP2	Epithelial membrane protein 2	Functions as a key regulator of cell membrane composition by regulating protein surface expression.

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)
EMP2	Other/Unknown	no		EMP-2, PMP22/EMP/MP20/Claudin, PMP22_EMP_MP20

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
lower lobe of lung	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EMP2	273	ubiquitous	marker	upper leg skin, upper arm skin, lower lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EMP2	625

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EMP2	P54851	94.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
plasma membrane raft assembly	1	8426.0×	0.001	EMP2
actin-mediated cell contraction	1	5617.3×	0.001	EMP2
regulation of vasculogenesis	1	5617.3×	0.001	EMP2
regulation of glomerular filtration	1	4213.0×	0.001	EMP2
regulation of kinase activity	1	4213.0×	0.001	EMP2
positive regulation of cardiac epithelial to mesenchymal transition	1	4213.0×	0.001	EMP2
natural killer cell proliferation	1	3370.4×	0.001	EMP2
heart formation	1	3370.4×	0.001	EMP2
membrane raft assembly	1	2808.7×	0.001	EMP2
regulation of endothelial cell migration	1	2106.5×	0.001	EMP2
embryonic process involved in female pregnancy	1	2106.5×	0.001	EMP2
bleb assembly	1	1532.0×	0.001	EMP2
blood vessel endothelial cell migration	1	1404.3×	0.001	EMP2
neutrophil migration	1	1404.3×	0.001	EMP2
regulation of cell-matrix adhesion	1	1296.3×	0.001	EMP2
positive regulation of integrin-mediated signaling pathway	1	1296.3×	0.001	EMP2
T cell mediated cytotoxicity	1	1123.5×	0.002	EMP2
positive regulation of cell-matrix adhesion	1	674.1×	0.002	EMP2
early endosome to late endosome transport	1	648.1×	0.002	EMP2
protein localization to cell surface	1	495.6×	0.003	EMP2
regulation of angiogenesis	1	421.3×	0.003	EMP2
embryo implantation	1	351.1×	0.004	EMP2
cell-matrix adhesion	1	163.6×	0.008	EMP2
actin filament organization	1	118.7×	0.010	EMP2
positive regulation of angiogenesis	1	115.4×	0.010	EMP2
protein localization to plasma membrane	1	108.7×	0.010	EMP2
cell adhesion	1	37.5×	0.029	EMP2
positive regulation of cell population proliferation	1	33.6×	0.031	EMP2
apoptotic process	1	28.7×	0.035	EMP2

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
EMP2	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	EMP2

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)
EMP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.