Glomerular disorder

Summary

Glomerular disorder (MONDO:0019722) is a disease (an umbrella term covering 7 Mondo subtypes) with 2 cohort genes and 4 clinical trials. Top therapeutic interventions include aliskiren, valsartan, and zigakibart.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glomerular disorder
Mondo ID	MONDO:0019722
EFO	EFO:1002049
Orphanet	93548
ICD-10-CM	N00-N08
NCIT	C120887
SNOMED CT	197679002
UMLS	C0268731
MedGen	451033
Anatomy (UBERON)	UBERON:0000074
Is cancer (heuristic)	no

Also known as: disease of renal glomerulus · disease or disorder of renal glomerulus · disorder of renal glomerulus · glomerulopathies · glomerulopathy · renal glomerulus disease · renal glomerulus disease or disorder

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

Related subtypes (56): renal hypertension, kidney failure, nephritis, impaired renal function disease, nephrocalcinosis, atheroembolism of kidney, renal artery disease, nephrosis, cystic kidney disease, anuria, stricture or kinking of ureter, proteinuria, renal infectious disease, diabetes insipidus, orthostatic proteinuria, kidney hypertrophy, chronic kidney disease, hydronephrosis, renal tubular transport disease, kidney cortex necrosis, kidney papillary necrosis, perinephritis, renal aminoaciduria, autosomal dominant progressive nephropathy with hypertension, nephrolithiasis, X-linked diffuse leiomyomatosis-Alport syndrome, tubulointerstitial nephritis and uveitis syndrome, distal renal tubular acidosis, oligomeganephronia, duplication of urethra, renal tubular dysgenesis, exstrophy-epispadias complex, fetal lower urinary tract obstruction, IgG4-related kidney disease, congenital primary megaureter, renal nutcracker syndrome, renal hypoplasia, renal dysplasia, congenital megacalycosis, congenital renal artery stenosis, kidney neoplasm, renal tubule disorder, pyonephrosis, Arnold stickler bourne syndrome, C1q nephropathy, hypertensive nephropathy, atypical Fanconi syndrome-neonatal hyperinsulinism syndrome, idiopathic non-lupus full-house nephropathy, lachiewicz sibley syndrome, crush syndrome, obstructive nephropathy, inherited kidney disorder, acute tubulointerstitial nephritis, kidney cortex disease, non-syndromic supernumerary kidneys, neonatal renal venous thrombosis

Subtypes (7): glomerulosclerosis, glomerulonephritis, fibronectin glomerulopathy, congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization, collagen type III glomerulopathy, immunotactoid or fibrillary glomerulopathy, podocytopathy

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
24455	NM_033380.3(COL4A5):c.1871G>A (p.Gly624Asp)	COL4A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
397521	NM_000091.5(COL4A3):c.2657-1G>T	COL4A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
COL4A5	Orphanet:1018	X-linked Alport syndrome-diffuse leiomyomatosis
COL4A5	Orphanet:653722	Digenic Alport syndrome
COL4A5	Orphanet:88917	X-linked Alport syndrome

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
COL4A3	HGNC:2204	ENSG00000169031	Q01955	Collagen alpha-3(IV) chain	clinvar
COL4A5	HGNC:2207	ENSG00000188153	P29400	Collagen alpha-5(IV) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.

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)
COL4A3	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A5	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold

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
pigmented layer of retina	1
retina	1
skeletal muscle tissue of biceps brachii	1
lower esophagus muscularis layer	1
mucosa of stomach	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL4A3	233	broad	marker	skeletal muscle tissue of biceps brachii, pigmented layer of retina, retina
COL4A5	267	ubiquitous	marker	mucosa of stomach, ventricular zone, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A5	1,738
COL4A3	1,671

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A3	Q01955	2
COL4A5	P29400	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	761.3×	1e-05	COL4A3, COL4A5
Fibronectin matrix formation	2	571.0×	1e-05	COL4A3, COL4A5
Crosslinking of collagen fibrils	2	571.0×	1e-05	COL4A3, COL4A5
Attachment of bacteria to epithelial cells	2	496.5×	1e-05	COL4A3, COL4A5
Laminin interactions	2	380.7×	2e-05	COL4A3, COL4A5
Collagen chain trimerization	2	259.6×	3e-05	COL4A3, COL4A5
Signaling by PDGF	2	253.8×	3e-05	COL4A3, COL4A5
NCAM1 interactions	2	248.3×	3e-05	COL4A3, COL4A5
Assembly of collagen fibrils and other multimeric structures	2	200.3×	4e-05	COL4A3, COL4A5
Collagen degradation	2	175.7×	5e-05	COL4A3, COL4A5
Collagen biosynthesis and modifying enzymes	2	170.4×	5e-05	COL4A3, COL4A5
Non-integrin membrane-ECM interactions	2	154.3×	5e-05	COL4A3, COL4A5
ECM proteoglycans	2	150.3×	5e-05	COL4A3, COL4A5
Integrin cell surface interactions	2	134.3×	6e-05	COL4A3, COL4A5
Regulation of expression of SLITs and ROBOs	1	34.6×	0.029	COL4A5

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
collagen-activated tyrosine kinase receptor signaling pathway	2	1296.3×	6e-06	COL4A3, COL4A5
collagen fibril organization	2	224.7×	1e-04	COL4A3, COL4A5
negative regulation of vascular endothelial cell proliferation	1	1685.2×	0.002	COL4A3
glomerular basement membrane development	1	766.0×	0.003	COL4A3
endothelial cell apoptotic process	1	648.1×	0.003	COL4A3
neuromuscular junction development	1	263.3×	0.007	COL4A5
negative regulation of angiogenesis	1	84.3×	0.019	COL4A3
sensory perception of sound	1	50.5×	0.027	COL4A3
cell surface receptor signaling pathway	1	32.0×	0.038	COL4A3
negative regulation of cell population proliferation	1	21.1×	0.052	COL4A3
cell adhesion	1	18.7×	0.053	COL4A3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
COL4A3	0	0
COL4A5	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	COL4A3, COL4A5

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)
COL4A3	0	—
COL4A5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT06858319	PHASE3	RECRUITING	Open-label Extension Study of Zigakibart in Adults With IgA Nephropathy.
NCT01016613	Not specified	RECRUITING	Clinical Phenotyping Resource and Biobank Core of the Michigan O’Brien Renal Center
NCT05294770	Not specified	UNKNOWN	Dietary Intervention in Obesity-related Glomerulopathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALISKIREN	4	1
VALSARTAN	4	1
ZIGAKIBART	3	1
CHEMBL115622	0	1