Primary membranoproliferative glomerulonephritis

Summary

Primary membranoproliferative glomerulonephritis (MONDO:0018904) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include bortezomib.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 16
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	16	Europe	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000793	Membranoproliferative glomerulonephritis	Very frequent (80-99%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000093	Proteinuria	Frequent (30-79%)
HP:0000100	Nephrotic syndrome	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0002907	Microscopic hematuria	Frequent (30-79%)
HP:0004746	Glomerular subendothelial electron-dense deposits	Frequent (30-79%)
HP:0005421	Decreased circulating complement C3 concentration	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0030888	C3 nephritic factor positivity	Frequent (30-79%)
HP:0001919	Acute kidney injury	Occasional (5-29%)
HP:0003073	Hypoalbuminemia	Occasional (5-29%)
HP:0003774	Stage 5 chronic kidney disease	Occasional (5-29%)
HP:0001658	Myocardial infarction	Very rare (<1-4%)
HP:0001977	Abnormal thrombosis	Very rare (<1-4%)
HP:0011510	Drusen	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	primary membranoproliferative glomerulonephritis
Mondo ID	MONDO:0018904
Orphanet	54370
GARD	0011982
MedDRA	10018370
Is cancer (heuristic)	no

Also known as: Mesangiocapillary glomerulonephritis · MPGN

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › nephritis › glomerulonephritis › primary membranoproliferative glomerulonephritis

Related subtypes (19): acute poststreptococcal glomerulonephritis, membranoproliferative glomerulonephritis, exudative glomerulonephritis, proliferative glomerulonephritis, focal embolic glomerulonephritis, anti-basement membrane glomerulonephritis, diffuse glomerulonephritis, subacute glomerulonephritis, mesangial proliferative glomerulonephritis, immune-complex glomerulonephritis, IgA glomerulonephritis, membranous glomerulonephritis, lupus nephritis, minimal change disease, granulomatosis with polyangiitis, rapidly progressive glomerulonephritis, Pauci-immune glomerulonephritis, immunotactoid glomerulopathy, autoimmune glomerulonephritis

Subtypes (3): membranoproliferative glomerulonephritis, X-linked, immunoglobulin-mediated membranoproliferative glomerulonephritis, complement 3 glomerulopathy

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1355757	NM_001845.6(COL4A1):c.4462+3A>G	COL4A1	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
COL4A1	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A1	Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1	Orphanet:481986	Familial schizencephaly
COL4A1	Orphanet:73229	HANAC syndrome
COL4A1	Orphanet:75326	Familial isolated retinal arteriolar tortuosity
COL4A1	Orphanet:899	Walker-Warburg syndrome
COL4A1	Orphanet:99810	Familial porencephaly

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
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL4A1	Collagen alpha-1(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: 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)
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold

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
placenta	1
right coronary artery	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL4A1	283	ubiquitous	marker	visceral pleura, placenta, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A1	2,909

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A1	P02462	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Anchoring fibril formation	1	761.3×	0.006	COL4A1
Scavenging by Class A Receptors	1	601.0×	0.006	COL4A1
Fibronectin matrix formation	1	571.0×	0.006	COL4A1
Crosslinking of collagen fibrils	1	571.0×	0.006	COL4A1
Attachment of bacteria to epithelial cells	1	496.5×	0.006	COL4A1
Laminin interactions	1	380.7×	0.007	COL4A1
Collagen chain trimerization	1	259.6×	0.007	COL4A1
Signaling by PDGF	1	253.8×	0.007	COL4A1
NCAM1 interactions	1	248.3×	0.007	COL4A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL4A1
Collagen degradation	1	175.7×	0.007	COL4A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL4A1
Non-integrin membrane-ECM interactions	1	154.3×	0.007	COL4A1
ECM proteoglycans	1	150.3×	0.007	COL4A1
Integrin cell surface interactions	1	134.3×	0.007	COL4A1

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
renal tubule morphogenesis	1	4213.0×	0.002	COL4A1
retinal blood vessel morphogenesis	1	2407.4×	0.002	COL4A1
collagen-activated tyrosine kinase receptor signaling pathway	1	1296.3×	0.003	COL4A1
blood vessel morphogenesis	1	802.5×	0.003	COL4A1
branching involved in blood vessel morphogenesis	1	526.6×	0.003	COL4A1
neuromuscular junction development	1	526.6×	0.003	COL4A1
basement membrane organization	1	510.7×	0.003	COL4A1
cellular response to amino acid stimulus	1	306.4×	0.004	COL4A1
collagen fibril organization	1	224.7×	0.005	COL4A1
epithelial cell differentiation	1	175.5×	0.006	COL4A1
brain development	1	79.5×	0.013	COL4A1

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
COL4A1	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	COL4A1

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)
COL4A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05383547	Not specified	UNKNOWN	Bortezomib for Treating Glomerular Diseases

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BORTEZOMIB	4	1