Steroid-resistant nephrotic syndrome

Summary

Steroid-resistant nephrotic syndrome (MONDO:0044765) is a disease with 14 cohort genes (2 GWAS associations across 4 studies) and 9 clinical trials. The dominant Reactome pathway is Anchoring fibril formation (3 cohort genes). Top therapeutic interventions include corticotropin, rituximab, and galactose.

At a glance

• Cohort genes: 14
• GWAS associations: 2
• ClinVar variants: 134
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	steroid-resistant nephrotic syndrome
Mondo ID	MONDO:0044765
NCIT	C122798
SNOMED CT	236381000
UMLS	C0403397
MedGen	588369
GARD	0027973
Is cancer (heuristic)	no

Also known as: nephrotic syndrome of childhood - steroid resistant · nephrotic syndrome, idiopathic, steroid-resistant · nephrotic syndrome, steroid-resistant, autosomal recessive · nephrotic syndrome-steroid-resistant · NPHS2 · steroid-resistant nephrotic syndrome

Data availability: 134 ClinVar variants · 2 GWAS associations (4 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › steroid-resistant nephrotic syndrome

Related subtypes (3): familial nephrotic syndrome, idiopathic nephrotic syndrome, nephrotic syndrome ocular anomalies

Subtypes (4): familial idiopathic steroid-resistant nephrotic syndrome, sporadic idiopathic steroid-resistant nephrotic syndrome, nephrotic syndrome 14, nephrotic syndrome of childhood - steroid sensitive

Genetics & variants

GWAS landscape

2 GWAS associations across 4 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs58384577	4e-07	APOL1	C	2.45
rs9274639	3e-06	HLA-DQB1	?	0.4

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90705047	Tu T	2026	41	0	Polygenic Risk Scores and HLA Class II Variants are Biomarkers of Corticosteroid Response in Childhood Nephrotic Syndrome.
GCST90705046	Tu T	2026	14	0	Polygenic Risk Scores and HLA Class II Variants are Biomarkers of Corticosteroid Response in Childhood Nephrotic Syndrome.
GCST90705044	Tu T	2026	0	0	Polygenic Risk Scores and HLA Class II Variants are Biomarkers of Corticosteroid Response in Childhood Nephrotic Syndrome.
GCST90705045	Tu T	2026	0	0	Polygenic Risk Scores and HLA Class II Variants are Biomarkers of Corticosteroid Response in Childhood Nephrotic Syndrome.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	0

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
3_prime_UTR_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs58384577	22	36267167	T>C	0.08	3_prime_UTR_variant	APOL1	4e-07	Tier 2: splice/UTR
rs9274639	6	32668369	T>A,C,G	0.05	regulatory_region_variant	HLA-DQB1	3e-06	Tier 3: regulatory

ClinVar germline variants

134 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 28 pathogenic/likely pathogenic, 16 conflicting classifications of pathogenicity, 16 pathogenic, 15 likely pathogenic, 11 likely benign, 5 benign, 4 benign/likely benign, 2 conflicting classifications of pathogenicity; risk factor

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
1068472	NM_014625.4(NPHS2):c.1032del (p.Phe344fs)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126418	NM_014625.4(NPHS2):c.868G>A (p.Val290Met)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370718	NM_014625.4(NPHS2):c.890C>T (p.Ala297Val)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371673	NM_014625.4(NPHS2):c.964C>T (p.Arg322Ter)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
447882	NM_014625.4(NPHS2):c.779T>A (p.Val260Glu)	AXDND1	Pathogenic	criteria provided, multiple submitters, no conflicts
5369	NM_014625.4(NPHS2):c.871C>T (p.Arg291Trp)	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
552884	NM_014625.4(NPHS2):c.873+2T>A	AXDND1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
555445	NM_014625.4(NPHS2):c.873+1G>A	AXDND1	Pathogenic	criteria provided, multiple submitters, no conflicts
180700	NM_173689.7(CRB2):c.1882C>T (p.Arg628Cys)	CRB2	Pathogenic/Likely pathogenic	no assertion criteria provided
180701	NM_173689.7(CRB2):c.3089_3104dup (p.Gly1036fs)	CRB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454556	NM_014625.4(NPHS2):c.738+1del	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1491797	NM_014625.4(NPHS2):c.928G>A (p.Glu310Lys)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188730	NM_014625.4(NPHS2):c.503G>A (p.Arg168His)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188823	NM_014625.4(NPHS2):c.855_856del (p.Arg286fs)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188892	NM_014625.4(NPHS2):c.586C>T (p.Arg196Ter)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188952	NM_014625.4(NPHS2):c.502C>T (p.Arg168Cys)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188990	NM_014625.4(NPHS2):c.948del (p.Ala317fs)	NPHS2	Pathogenic	criteria provided, multiple submitters, no conflicts
2030308	NM_014625.4(NPHS2):c.738+1G>C	NPHS2	Pathogenic	criteria provided, multiple submitters, no conflicts
2183604	NM_014625.4(NPHS2):c.483del (p.Tyr162fs)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2502066	NM_014625.4(NPHS2):c.705_713del (p.Leu236_Arg238del)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677345	NM_014625.4(NPHS2):c.293_294del (p.Leu98fs)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370159	NM_014625.4(NPHS2):c.643C>T (p.Gln215Ter)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370340	NM_014625.4(NPHS2):c.685C>T (p.Arg229Ter)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4059073	NM_014625.4(NPHS2):c.377del (p.Lys126fs)	NPHS2	Pathogenic	criteria provided, single submitter
447876	NM_014625.4(NPHS2):c.104dup (p.Arg36fs)	NPHS2	Pathogenic	criteria provided, multiple submitters, no conflicts
4815732	NM_014625.4(NPHS2):c.378+1G>T	NPHS2	Pathogenic	criteria provided, single submitter
495108	NM_014625.4(NPHS2):c.156del (p.Thr53fs)	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
504890	NM_014625.4(NPHS2):c.535-1G>T	NPHS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 31 · 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
KAT2B	Limited	Autosomal recessive	steroid-resistant nephrotic syndrome

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCAL1	Orphanet:1830	Schimke immuno-osseous dysplasia
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
NPHS2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
AVIL	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
CRB2	Orphanet:443988	Ventriculomegaly-cystic kidney disease
CRB2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COL4A3	Orphanet:653722	Digenic Alport syndrome
COL4A3	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COL4A3	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A3	Orphanet:88919	Autosomal recessive Alport syndrome
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome
COL4A5	Orphanet:1018	X-linked Alport syndrome-diffuse leiomyomatosis
COL4A5	Orphanet:653722	Digenic Alport syndrome
COL4A5	Orphanet:88917	X-linked Alport syndrome
GLA	Orphanet:324	Fabry disease
APOL1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
NPHS1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
NPHS1	Orphanet:839	Congenital nephrotic syndrome, Finnish type
PAX2	Orphanet:1475	Renal coloboma syndrome
PAX2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PAX2	Orphanet:97362	Renal hypoplasia, bilateral

Cohort genes → proteins

14 cohort genes, 14 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KAT2B	HGNC:8638	ENSG00000114166	Q92831	Histone acetyltransferase KAT2B	gencc
SMARCAL1	HGNC:11102	ENSG00000138375	Q9NZC9	SNF2 related chromatin remodeling annealing helicase 1	clinvar
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	clinvar
NPHS2	HGNC:13394	ENSG00000116218	Q9NP85	Podocin	clinvar
AVIL	HGNC:14188	ENSG00000135407	O75366	Advillin	clinvar
CRB2	HGNC:18688	ENSG00000148204	Q5IJ48	Protein crumbs homolog 2	clinvar
COL4A3	HGNC:2204	ENSG00000169031	Q01955	Collagen alpha-3(IV) chain	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
COL4A5	HGNC:2207	ENSG00000188153	P29400	Collagen alpha-5(IV) chain	clinvar
AXDND1	HGNC:26564	ENSG00000162779	Q5T1B0	Axonemal dynein light chain domain-containing protein 1	clinvar
GLA	HGNC:4296	ENSG00000102393	P06280	Alpha-galactosidase A	clinvar
APOL1	HGNC:618	ENSG00000100342	O14791	Apolipoprotein L1	clinvar
NPHS1	HGNC:7908	ENSG00000161270	O60500	Nephrin	clinvar
PAX2	HGNC:8616	ENSG00000075891	Q02962	Paired box protein Pax-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KAT2B	Histone acetyltransferase KAT2B	Functions as a histone acetyltransferase (HAT) to promote transcriptional activation.
SMARCAL1	SNF2 related chromatin remodeling annealing helicase 1	ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
NPHS2	Podocin	Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton.
AVIL	Advillin	Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling.
CRB2	Protein crumbs homolog 2	Apical polarity protein that plays a central role during the epithelial-to-mesenchymal transition (EMT) at gastrulation, when newly specified mesodermal cells move inside the embryo.
COL4A3	Collagen alpha-3(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A5	Collagen alpha-5(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
AXDND1	Axonemal dynein light chain domain-containing protein 1	May be essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping and sperm flagellum assembly.
GLA	Alpha-galactosidase A	Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome.
APOL1	Apolipoprotein L1	May play a role in lipid exchange and transport throughout the body.
NPHS1	Nephrin	Seems to play a role in the development or function of the kidney glomerular filtration barrier.
PAX2	Paired box protein Pax-2	Transcription factor that may have a role in kidney cell differentiation.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 9 · Druggable fraction: 0.21

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	2.1×	0.515
Enzyme (other)	2	1.7×	0.515
Other/Unknown	9	1.1×	0.515
Transcription factor	2	1.2×	0.519

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KAT2B	Enzyme (other)	yes	2.3.1.48	GNAT_dom, Bromodomain, PCAF_N
SMARCAL1	Other/Unknown	no		SNF2_N, Helicase_C-like, HARP_dom
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
NPHS2	Other/Unknown	no		Band_7, Stomatin_HflK_fam, Band_7/stomatin-like_CS
AVIL	Other/Unknown	no		Villin_headpiece, Villin/Gelsolin, Gelsolin-like_dom
CRB2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
COL4A3	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A5	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
AXDND1	Other/Unknown	no		Axonemal_dynein_light_chain, Axonemal_dynein_LC_domain
GLA	Enzyme (other)	yes	3.2.1.22	Glyco_hydro_27/36_CS, Glyco_hydro_27, Glyco_hydro_b
APOL1	Other/Unknown	no		ApoL
NPHS1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
PAX2	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C

Expression context

Cohort genes with no expression data: 0.

14 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)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	2
metanephric glomerulus	2
renal glomerulus	2
ventricular zone	2
pigmented layer of retina	2
metanephros cortex	2
renal medulla	2
lateral globus pallidus	1
trabecular bone tissue	1
primordial germ cell in gonad	1
stromal cell of endometrium	1
sural nerve	1
germinal epithelium of ovary	1
kidney epithelium	1
cerebellar hemisphere	1
dorsal root ganglion	1
gastrocnemius	1
ganglionic eminence	1
male germ line stem cell (sensu Vertebrata) in testis	1
retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KAT2B	294	ubiquitous	marker	lateral globus pallidus, trabecular bone tissue, buccal mucosa cell
SMARCAL1	264	ubiquitous	marker	primordial germ cell in gonad, stromal cell of endometrium, sural nerve
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
NPHS2	47	tissue_specific	marker	renal glomerulus, metanephric glomerulus, kidney epithelium
AVIL	217	tissue_specific	marker	dorsal root ganglion, cerebellar hemisphere, gastrocnemius
CRB2	99	broad	marker	ventricular zone, ganglionic eminence, male germ line stem cell (sensu Vertebrata) in testis
COL4A3	233	broad	marker	skeletal muscle tissue of biceps brachii, pigmented layer of retina, retina
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
COL4A5	267	ubiquitous	marker	mucosa of stomach, ventricular zone, lower esophagus muscularis layer
AXDND1	161	tissue_specific	marker	sperm, left testis, right testis
GLA	263	ubiquitous	marker	pancreatic ductal cell, monocyte, mononuclear cell
APOL1	252	ubiquitous	marker	gall bladder, right lobe of liver, liver
NPHS1	147	tissue_specific	marker	buccal mucosa cell, body of pancreas, vena cava
PAX2	92	broad	marker	metanephros cortex, renal medulla, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KAT2B	4,410
WT1	3,938
SMARCAL1	2,899
PAX2	2,208
GLA	1,826
NPHS2	1,811
COL4A5	1,738
NPHS1	1,690
COL4A3	1,671
CRB2	1,640

Intra-cohort edges

A	B	Sources
APOL1	NPHS1	string_interaction
APOL1	NPHS2	string_interaction
COL4A3	COL4A4	string_interaction
COL4A3	NPHS1	string_interaction
COL4A3	NPHS2	string_interaction
COL4A4	COL4A5	string_interaction
COL4A4	NPHS1	string_interaction
COL4A4	NPHS2	string_interaction
COL4A5	NPHS1	string_interaction
COL4A5	NPHS2	string_interaction
NPHS1	NPHS2	biogrid_interaction, string_interaction
NPHS1	PAX2	string_interaction
NPHS1	WT1	string_interaction
NPHS2	WT1	string_interaction
PAX2	WT1	string_interaction

Structural data

PDB: 11 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GLA	P06280	31
WT1	P19544	28
KAT2B	Q92831	25
APOL1	O14791	5
COL4A3	Q01955	2
COL4A4	P53420	2
COL4A5	P29400	2
SMARCAL1	Q9NZC9	1
AVIL	O75366	1
CRB2	Q5IJ48	1
NPHS1	O60500	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NPHS2	Q9NP85	75.00
AXDND1	Q5T1B0	70.90
PAX2	Q02962	61.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 90. Enrichment computed across 14 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring fibril formation	3	228.4×	2e-05	COL4A3, COL4A4, COL4A5
Fibronectin matrix formation	3	171.3×	2e-05	COL4A3, COL4A4, COL4A5
Crosslinking of collagen fibrils	3	171.3×	2e-05	COL4A3, COL4A4, COL4A5
Attachment of bacteria to epithelial cells	3	149.0×	2e-05	COL4A3, COL4A4, COL4A5
Laminin interactions	3	114.2×	3e-05	COL4A3, COL4A4, COL4A5
Collagen chain trimerization	3	77.9×	8e-05	COL4A3, COL4A4, COL4A5
Signaling by PDGF	3	76.1×	8e-05	COL4A3, COL4A4, COL4A5
NCAM1 interactions	3	74.5×	8e-05	COL4A3, COL4A4, COL4A5
Assembly of collagen fibrils and other multimeric structures	3	60.1×	1e-04	COL4A3, COL4A4, COL4A5
Collagen degradation	3	52.7×	2e-04	COL4A3, COL4A4, COL4A5
Collagen biosynthesis and modifying enzymes	3	51.1×	2e-04	COL4A3, COL4A4, COL4A5
Non-integrin membrane-ECM interactions	3	46.3×	2e-04	COL4A3, COL4A4, COL4A5
ECM proteoglycans	3	45.1×	2e-04	COL4A3, COL4A4, COL4A5
Integrin cell surface interactions	3	40.3×	3e-04	COL4A3, COL4A4, COL4A5
Nephron development	2	175.7×	3e-04	WT1, PAX2
Nephrin family interactions	2	95.2×	0.001	NPHS2, NPHS1
Formation of intermediate mesoderm	1	142.8×	0.037	PAX2
Regulation of FOXO transcriptional activity by acetylation	1	114.2×	0.044	KAT2B
Scavenging of heme from plasma	1	87.8×	0.052	APOL1
RUNX3 regulates NOTCH signaling	1	81.6×	0.052	KAT2B
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	76.1×	0.052	KAT2B
Regulation of beta-cell development	1	71.4×	0.052	KAT2B
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	71.4×	0.052	KAT2B
Transcriptional regulation of testis differentiation	1	71.4×	0.052	WT1
Physiological factors	1	67.2×	0.053	KAT2B
Formation of the nephric duct	1	63.4×	0.054	PAX2
NOTCH4 Intracellular Domain Regulates Transcription	1	57.1×	0.058	KAT2B
Binding and Uptake of Ligands by Scavenger Receptors	1	54.4×	0.058	APOL1
Signaling by NOTCH3	1	51.9×	0.058	KAT2B
Signaling by NOTCH4	1	49.6×	0.058	KAT2B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glomerular basement membrane development	4	437.7×	2e-08	WT1, COL4A3, COL4A4, NPHS1
metanephric epithelium development	2	481.5×	6e-04	WT1, PAX2
metanephric mesenchyme development	2	343.9×	8e-04	WT1, PAX2
mesenchymal to epithelial transition	2	218.9×	0.001	WT1, PAX2
collagen fibril organization	3	48.1×	0.001	COL4A3, COL4A4, COL4A5
collagen-activated tyrosine kinase receptor signaling pathway	2	185.2×	0.002	COL4A3, COL4A5
ingression involved in gastrulation with mouth forming second	1	1203.7×	0.010	CRB2
optic chiasma development	1	1203.7×	0.010	PAX2
negative regulation of metanephric glomerular mesangial cell proliferation	1	1203.7×	0.010	WT1
regulation of diacylglycerol biosynthetic process	1	1203.7×	0.010	AVIL
positive regulation of optic nerve formation	1	1203.7×	0.010	PAX2
optic cup morphogenesis involved in camera-type eye development	1	601.9×	0.010	PAX2
regulation of animal organ formation	1	601.9×	0.010	WT1
optic nerve structural organization	1	601.9×	0.010	PAX2
regulation of metanephros size	1	601.9×	0.010	PAX2
adrenal cortex formation	1	601.9×	0.010	WT1
slit diaphragm assembly	1	601.9×	0.010	NPHS1
pronephric field specification	1	601.9×	0.010	PAX2
negative regulation of nitric-oxide synthase activity	1	601.9×	0.010	GLA
visceral serous pericardium development	1	601.9×	0.010	WT1
posterior mesonephric tubule development	1	601.9×	0.010	WT1
metanephric podocyte development	1	601.9×	0.010	NPHS2
obsolete negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis	1	601.9×	0.010	PAX2
obsolete negative regulation of apoptotic process involved in metanephric collecting duct development	1	601.9×	0.010	PAX2
obsolete negative regulation of apoptotic process involved in metanephric nephron tubule development	1	601.9×	0.010	PAX2
negative regulation of rRNA processing	1	601.9×	0.010	KAT2B
positive regulation of metanephric DCT cell differentiation	1	601.9×	0.010	PAX2
positive regulation of metanephric ureteric bud development	1	601.9×	0.010	WT1
branching involved in ureteric bud morphogenesis	2	52.3×	0.010	WT1, PAX2
camera-type eye development	2	51.2×	0.010	WT1, PAX2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 12

Druggability breadth: 8 of 14 evidence-associated genes (57%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GLA	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GLA	62	4
KAT2B	3	3
SMARCAL1	0	0
WT1	0	0
NPHS2	0	0
AVIL	0	0
CRB2	0	0
COL4A3	0	0
COL4A4	0	0
COL4A5	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	GLA
METHYSERGIDE	4	GLA
MIGALASTAT	4	GLA
PINACIDIL ANHYDROUS	4	GLA
DOXAZOSIN MESYLATE	4	GLA
AMPICILLIN SODIUM	4	GLA
PHENOXYBENZAMINE HYDROCHLORIDE	4	GLA
METHYSERGIDE MALEATE	4	GLA
ACRISORCIN	4	GLA
NOMIFENSINE MALEATE	4	GLA
INAMRINONE	4	GLA
AMILORIDE HYDROCHLORIDE	4	GLA
PHENOL	4	GLA
FLUPHENAZINE HYDROCHLORIDE	4	GLA
PRAZOSIN HYDROCHLORIDE	4	GLA
PSEUDOEPHEDRINE	4	GLA
PHENYTOIN SODIUM	4	GLA
RIBAVIRIN	4	GLA
SOTALOL HYDROCHLORIDE	4	GLA
DIGOXIN	4	GLA
PRAZOSIN	4	GLA
DOMPERIDONE	4	GLA
CIMETIDINE	4	GLA
MASOPROCOL	4	GLA
METHOTREXATE	4	GLA
AMSACRINE	4	GLA
LANSOPRAZOLE	4	GLA
PINDOLOL	4	GLA
NIMESULIDE	4	GLA
TRIAMTERENE	4	GLA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KAT2B	217	Binding:217
GLA	114	Binding:104, Functional:10
APOL1	4	Binding:4
PAX2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT2B	2.3.1.48	histone acetyltransferase
GLA	3.2.1.22	alpha-galactosidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
KAT2B	217
GLA	114

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
CLOTRIMAZOLE	4	GLA
METHYSERGIDE	4	GLA
MIGALASTAT	4	GLA
PINACIDIL ANHYDROUS	4	GLA
DOXAZOSIN MESYLATE	4	GLA
AMPICILLIN SODIUM	4	GLA
PHENOXYBENZAMINE HYDROCHLORIDE	4	GLA
METHYSERGIDE MALEATE	4	GLA
ACRISORCIN	4	GLA
NOMIFENSINE MALEATE	4	GLA
INAMRINONE	4	GLA
AMILORIDE HYDROCHLORIDE	4	GLA
PHENOL	4	GLA
FLUPHENAZINE HYDROCHLORIDE	4	GLA
PRAZOSIN HYDROCHLORIDE	4	GLA
PSEUDOEPHEDRINE	4	GLA
PHENYTOIN SODIUM	4	GLA
RIBAVIRIN	4	GLA
SOTALOL HYDROCHLORIDE	4	GLA
DIGOXIN	4	GLA
PRAZOSIN	4	GLA
DOMPERIDONE	4	GLA
CIMETIDINE	4	GLA
MASOPROCOL	4	GLA
METHOTREXATE	4	GLA
AMSACRINE	4	GLA
LANSOPRAZOLE	4	GLA
PINDOLOL	4	GLA
NIMESULIDE	4	GLA
TRIAMTERENE	4	GLA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GLA
B	Phased (≥1) drug, not yet approved	1	KAT2B
C	Druggable family + PDB, no drug	1	NPHS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	11	SMARCAL1, WT1, NPHS2, AVIL, CRB2, COL4A3, COL4A4, COL4A5, AXDND1, APOL1 (+1 more)

Undrugged target profiles

12 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SMARCAL1	0	—
WT1	0	—
NPHS2	0	—
AVIL	0	—
CRB2	0	—
COL4A3	0	—
COL4A4	0	—
COL4A5	0	—
AXDND1	0	—
APOL1	4	—
NPHS1	0	—
PAX2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	1
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03408405	PHASE4	WITHDRAWN	ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children
NCT01716442	PHASE2/PHASE3	UNKNOWN	Rituximab Trial for Pediatric Nephrotic Syndrome
NCT07003438	EARLY_PHASE1	NOT_YET_RECRUITING	Study on the Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Steroid - Dependent /Steroid-resistant Nephrotic Syndrome in Children
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06162546	Not specified	RECRUITING	ARREST-NEPHROSIS - Austrian Resistant Nephrotic Syndrome Treatment Response Registry and Biobank
NCT06792448	Not specified	NOT_YET_RECRUITING	Biomarkers and Outcome Predictors of Pediatric Nephrotic Syndrome: A Genetic, Transcriptomic, and Secretome Multiomics Study
NCT00883636	Not specified	TERMINATED	Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis
NCT01113385	Not specified	COMPLETED	Oral Galactose in Children With Steroid Resistant Nephrotic Syndrome
NCT03235128	Not specified	UNKNOWN	Clinical Significance of Assesment of Serum miRNA-30a in Childhood Nephrotic Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CORTICOTROPIN	4	1
RITUXIMAB	4	1
GALACTOSE	3	1
D-GALACTOSE	0	1