Glomerulosclerosis

Summary

Glomerulosclerosis (MONDO:0000490) is a disease with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include magnesium and ilacirnon.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glomerulosclerosis
Mondo ID	MONDO:0000490
DOID	DOID:0050851
ICD-11	2068645853
NCIT	C120888
SNOMED CT	197661001
UMLS	C0178664
MedGen	61248
GARD	0022776
Is cancer (heuristic)	no

Also known as: glomerular sclerosis

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › glomerular disorder › glomerulosclerosis

Related subtypes (6): glomerulonephritis, fibronectin glomerulopathy, congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization, collagen type III glomerulopathy, immunotactoid or fibrillary glomerulopathy, podocytopathy

Subtypes (2): renal fibrosis, focal segmental glomerulosclerosis

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
156297	NM_000278.5(PAX2):c.76dup (p.Val26fs)	PAX2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PAX2	Orphanet:1475	Renal coloboma syndrome
PAX2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PAX2	Orphanet:97362	Renal hypoplasia, bilateral

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
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)
PAX2	Paired box protein Pax-2	Transcription factor that may have a role in kidney cell differentiation.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX2	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C

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
adult mammalian kidney	1
metanephros cortex	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX2	92	broad	marker	metanephros cortex, renal medulla, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX2	2,208

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PAX2	Q02962	61.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Formation of intermediate mesoderm	1	1427.5×	0.002	PAX2
Nephron development	1	878.5×	0.002	PAX2
Formation of the nephric duct	1	634.4×	0.002	PAX2
Formation of the ureteric bud	1	496.5×	0.002	PAX2

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
optic chiasma development	1	16852.0×	7e-04	PAX2
positive regulation of optic nerve formation	1	16852.0×	7e-04	PAX2
optic cup morphogenesis involved in camera-type eye development	1	8426.0×	7e-04	PAX2
optic nerve structural organization	1	8426.0×	7e-04	PAX2
regulation of metanephros size	1	8426.0×	7e-04	PAX2
pronephric field specification	1	8426.0×	7e-04	PAX2
obsolete negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis	1	8426.0×	7e-04	PAX2
obsolete negative regulation of apoptotic process involved in metanephric collecting duct development	1	8426.0×	7e-04	PAX2
obsolete negative regulation of apoptotic process involved in metanephric nephron tubule development	1	8426.0×	7e-04	PAX2
positive regulation of metanephric DCT cell differentiation	1	8426.0×	7e-04	PAX2
nephric duct formation	1	5617.3×	8e-04	PAX2
positive regulation of metanephric glomerulus development	1	5617.3×	8e-04	PAX2
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	1	5617.3×	8e-04	PAX2
ureter maturation	1	4213.0×	8e-04	PAX2
metanephric distal convoluted tubule development	1	4213.0×	8e-04	PAX2
optic nerve morphogenesis	1	3370.4×	8e-04	PAX2
vestibulocochlear nerve formation	1	3370.4×	8e-04	PAX2
metanephric mesenchymal cell differentiation	1	3370.4×	8e-04	PAX2
metanephric epithelium development	1	3370.4×	8e-04	PAX2
metanephric nephron tubule formation	1	3370.4×	8e-04	PAX2
regulation of metanephric nephron tubule epithelial cell differentiation	1	3370.4×	8e-04	PAX2
positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	2808.7×	9e-04	PAX2
ureter development	1	2808.7×	9e-04	PAX2
pronephros development	1	2407.4×	9e-04	PAX2
metanephric mesenchyme development	1	2407.4×	9e-04	PAX2
mesenchymal to epithelial transition involved in metanephros morphogenesis	1	2106.5×	0.001	PAX2
mesodermal cell fate specification	1	2106.5×	0.001	PAX2
retinal pigment epithelium development	1	1685.2×	0.001	PAX2
metanephric collecting duct development	1	1685.2×	0.001	PAX2
mesonephros development	1	1532.0×	0.001	PAX2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PAX2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PAX2	1	Binding:1

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	PAX2

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)
PAX2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03536754	PHASE2	COMPLETED	A Study of CCX140-B in Subjects With FSGS
NCT04950114	PHASE2	TERMINATED	An Open-Label, Long-term Study of GFB-887 in Patients With Glomerular Kidney Diseases
NCT04924712	Not specified	RECRUITING	INS, B Cells and Microbiota
NCT06766786	Not specified	COMPLETED	Magnesium Supplementation in Simultaneous Pancreas-Kidney Transplantation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MAGNESIUM	3	1
ILACIRNON	2	1