Nephrotic syndrome, type 24

Summary

Nephrotic syndrome, type 24 (MONDO:0031008) is a disease caused by DAAM2 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: DAAM2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.2582	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0003073	Hypoalbuminemia	Very frequent (80-99%)
HP:0003119	Abnormal circulating lipid concentration	Very frequent (80-99%)
HP:0031265	Abnormal podocyte morphology	Very frequent (80-99%)
HP:0000097	Focal segmental glomerulosclerosis	Frequent (30-79%)
HP:0000969	Edema	Frequent (30-79%)
HP:0002155	Hypertriglyceridemia	Frequent (30-79%)
HP:0003124	Hypercholesterolemia	Frequent (30-79%)
HP:0012579	Minimal change glomerulonephritis	Frequent (30-79%)
HP:0100724	Hypercoagulability	Frequent (30-79%)
HP:0001919	Acute kidney injury	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0003774	Stage 5 chronic kidney disease	Occasional (5-29%)
HP:0011947	Respiratory tract infection	Occasional (5-29%)
HP:0012590	Abnormal urine output	Occasional (5-29%)
HP:0031504	Foamy urine	Occasional (5-29%)
HP:0100539	Periorbital edema	Occasional (5-29%)
HP:0001510	Growth delay	Very rare (<1-4%)
HP:0001967	Diffuse mesangial sclerosis	Very rare (<1-4%)
HP:0002204	Pulmonary embolism	Very rare (<1-4%)
HP:0002586	Peritonitis	Very rare (<1-4%)
HP:0004936	Venous thrombosis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 24
Mondo ID	MONDO:0031008
OMIM	619263
Orphanet	567548
DOID	DOID:0061194
UMLS	C5543267
MedGen	1781068
GARD	0018003
Is cancer (heuristic)	no

Also known as: idiopathic SRNS · idiopathic steroid-resistant nephrotic syndrome · NPHS24

Data availability: 14 ClinVar variants · 2 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 24

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, IIa 26, nephrotic syndrome, type 17, 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

14 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1054666	NM_001201427.2(DAAM2):c.361G>C (p.Glu121Gln)	DAAM2	Pathogenic	no assertion criteria provided
1054669	NM_001201427.2(DAAM2):c.1004G>A (p.Arg335Gln)	DAAM2	Pathogenic	no assertion criteria provided
1054670	NM_001201427.2(DAAM2):c.1333C>T (p.Arg445Ter)	DAAM2	Pathogenic	no assertion criteria provided
3391004	NM_001201427.2(DAAM2):c.196C>T (p.Arg66Ter)	DAAM2	Likely pathogenic	criteria provided, single submitter
4278020	NM_001201427.2(DAAM2):c.3058G>T (p.Gly1020Ter)	DAAM2	Likely pathogenic	criteria provided, single submitter
1054668	NM_001201427.2(DAAM2):c.1745C>A (p.Pro582His)	DAAM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1054671	NM_001201427.2(DAAM2):c.3083C>T (p.Ser1028Leu)	DAAM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705482	NM_001201427.2(DAAM2):c.1003C>T (p.Arg335Trp)	DAAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2241639	NM_001201427.2(DAAM2):c.2026C>T (p.Arg676Trp)	DAAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582327	NM_001201427.2(DAAM2):c.220C>A (p.Pro74Thr)	DAAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582404	NM_001201427.2(DAAM2):c.2203G>A (p.Glu735Lys)	DAAM2	Uncertain significance	criteria provided, single submitter
2582484	NM_001201427.2(DAAM2):c.2279A>G (p.Gln760Arg)	DAAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4078454	NM_001201427.2(DAAM2):c.2945_2957del (p.Lys982fs)	DAAM2	Uncertain significance	criteria provided, single submitter
4237286	NM_001201427.2(DAAM2):c.2968C>T (p.Arg990Cys)	DAAM2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
DAAM2	Strong	Autosomal recessive	nephrotic syndrome, type 24	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DAAM2	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
DAAM2	HGNC:18143	ENSG00000146122	Q86T65	Disheveled-associated activator of morphogenesis 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DAAM2	Disheveled-associated activator of morphogenesis 2	Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system.

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)
DAAM2	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-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
corpus callosum	1
inferior vagus X ganglion	1
middle frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DAAM2	276	ubiquitous	marker	corpus callosum, middle frontal gyrus, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DAAM2	2,071

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DAAM2	Q86T65	80.02

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
regulation of non-canonical Wnt signaling pathway	1	8426.0×	0.002	DAAM2
podocyte cell migration	1	2407.4×	0.002	DAAM2
dorsal spinal cord development	1	1685.2×	0.002	DAAM2
negative regulation of oligodendrocyte differentiation	1	1123.5×	0.002	DAAM2
regulation of filopodium assembly	1	1053.2×	0.002	DAAM2
regulation of actin filament polymerization	1	581.1×	0.003	DAAM2
regulation of canonical Wnt signaling pathway	1	543.6×	0.003	DAAM2
determination of left/right symmetry	1	255.3×	0.006	DAAM2
regulation of actin cytoskeleton organization	1	157.5×	0.008	DAAM2
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.008	DAAM2
Wnt signaling pathway	1	99.7×	0.012	DAAM2
actin cytoskeleton organization	1	79.1×	0.014	DAAM2
positive regulation of cell migration	1	61.7×	0.016	DAAM2

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
DAAM2	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	DAAM2

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)
DAAM2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.