Nephrotic syndrome, type 21

Summary

Nephrotic syndrome, type 21 (MONDO:0032826) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 21
Mondo ID	MONDO:0032826
OMIM	618594
DOID	DOID:0112267
UMLS	C5231498
MedGen	1684676
GARD	0027944
Is cancer (heuristic)	no

Also known as: NPHS21

Data availability: 21 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › nephrotic syndrome, type 21

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 18, nephrotic syndrome, type 19, 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

21 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
684648	NM_006576.4(AVIL):c.1273C>A (p.Leu425Met)	AVIL	Pathogenic	no assertion criteria provided
684649	NM_006576.4(AVIL):c.1337G>A (p.Arg446His)	AVIL	Pathogenic	no assertion criteria provided
1810257	NM_006576.4(AVIL):c.595C>T (p.Arg199Ter)	AVIL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4845723	NM_006576.4(AVIL):c.505A>T (p.Lys169Ter)	AVIL	Likely pathogenic	criteria provided, single submitter
684650	NM_006576.4(AVIL):c.404G>A (p.Arg135Gln)	AVIL	Likely pathogenic	criteria provided, single submitter
684651	NM_006576.4(AVIL):c.1964dup (p.Phe656fs)	AVIL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
418526	NM_005726.6(TSFM):c.644C>T (p.Ser215Phe)	TSFM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1691301	NM_006576.4(AVIL):c.431A>T (p.Asn144Ile)	AVIL	Uncertain significance	criteria provided, single submitter
1691303	NM_006576.4(AVIL):c.1204A>G (p.Ile402Val)	AVIL	Uncertain significance	criteria provided, single submitter
2386846	NM_006576.4(AVIL):c.2331C>A (p.Asn777Lys)	AVIL	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439445	NM_006576.4(AVIL):c.2250T>A (p.Asn750Lys)	AVIL	Uncertain significance	criteria provided, single submitter
2439446	NM_006576.4(AVIL):c.66+9G>A	AVIL	Uncertain significance	criteria provided, single submitter
2439447	NM_006576.4(AVIL):c.812dup (p.Leu272fs)	AVIL	Uncertain significance	criteria provided, single submitter
2442084	NM_006576.4(AVIL):c.121G>A (p.Asp41Asn)	AVIL	Uncertain significance	criteria provided, single submitter
2515403	NM_006576.4(AVIL):c.749T>C (p.Ile250Thr)	AVIL	Uncertain significance	criteria provided, multiple submitters, no conflicts
3068057	NM_006576.4(AVIL):c.1285A>G (p.Thr429Ala)	AVIL	Uncertain significance	criteria provided, single submitter
3780682	NM_006576.4(AVIL):c.1241G>A (p.Trp414Ter)	AVIL	Uncertain significance	criteria provided, single submitter
4078092	NM_006576.4(AVIL):c.1955G>A (p.Trp652Ter)	AVIL	Uncertain significance	criteria provided, single submitter
4278441	NM_006576.4(AVIL):c.1330C>T (p.Gln444Ter)	AVIL	Uncertain significance	criteria provided, single submitter
4814067	NM_006576.4(AVIL):c.1444C>T (p.Pro482Ser)	AVIL	Uncertain significance	criteria provided, single submitter
1192376	NM_006576.4(AVIL):c.610A>G (p.Lys204Glu)	AVIL	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
AVIL	Limited	Unknown	nephrotic syndrome, type 21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AVIL	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
TSFM	Orphanet:168566	Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3

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
AVIL	HGNC:14188	ENSG00000135407	O75366	Advillin	gencc,clinvar
TSFM	HGNC:12367	ENSG00000123297	P43897	Elongation factor Ts, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AVIL	Advillin	Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling.
TSFM	Elongation factor Ts, mitochondrial	Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP.

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)
AVIL	Other/Unknown	no		Villin_headpiece, Villin/Gelsolin, Gelsolin-like_dom
TSFM	Other/Unknown	no		Transl_elong_EFTs/EF1B, UBA-like_sf, Transl_elong_EFTs/EF1B_dimer

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 hemisphere	1
dorsal root ganglion	1
gastrocnemius	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AVIL	217	tissue_specific	marker	dorsal root ganglion, cerebellar hemisphere, gastrocnemius
TSFM	134	ubiquitous	marker	right adrenal gland, left adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSFM	3,286
AVIL	941

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AVIL	O75366	1
TSFM	P43897	1

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
Mitochondrial translation elongation	1	126.9×	0.008	TSFM

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
regulation of diacylglycerol biosynthetic process	1	8426.0×	0.001	AVIL
mitochondrial translational elongation	1	2106.5×	0.002	TSFM
actin filament severing	1	601.9×	0.005	AVIL
barbed-end actin filament capping	1	401.2×	0.005	AVIL
actin polymerization or depolymerization	1	383.0×	0.005	AVIL
positive regulation of lamellipodium assembly	1	300.9×	0.006	AVIL
positive regulation of neuron projection development	1	68.5×	0.021	AVIL
actin filament organization	1	59.3×	0.021	AVIL
cilium assembly	1	36.8×	0.030	AVIL
nervous system development	1	23.0×	0.043	AVIL

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
AVIL	0	0
TSFM	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	AVIL, TSFM

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)
AVIL	0	—
TSFM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.