Dense deposit disease

Summary

Dense deposit disease (MONDO:0019736) is a disease with 2 cohort genes and 15 clinical trials. Top therapeutic interventions include pegcetacoplan, danicopan, and enalapril.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Clinical trials: 15

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.25	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	dense deposit disease
Mondo ID	MONDO:0019736
Orphanet	93571
NCIT	C123039
SNOMED CT	722760002
UMLS	C0268743
MedGen	124345
GARD	0008555
Is cancer (heuristic)	no

Also known as: glomerulonephritis membranoproliferative type 2 · membranoproliferative glomerulonephritis type 2 · membranoproliferative glomerulonephritis type II · Mesangiocapillary glomerulonephritis type 2 · MPGN 2

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › nephritis › glomerulonephritis › primary membranoproliferative glomerulonephritis › complement 3 glomerulopathy › dense deposit disease

Related subtypes (2): complement factor H deficiency, C3 glomerulonephritis

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 9 · 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
CFH	Supportive	Autosomal recessive	dense deposit disease	9
CFHR1	Supportive	Autosomal recessive	dense deposit disease	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFH	Orphanet:200421	Immunodeficiency with factor H anomaly
CFH	Orphanet:244242	HELLP syndrome
CFH	Orphanet:244275	De novo thrombotic microangiopathy after kidney transplantation
CFH	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
CFH	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
CFH	Orphanet:75376	Familial drusen
CFH	Orphanet:93571	Dense deposit disease
CFHR1	Orphanet:329931	C3 glomerulonephritis
CFHR1	Orphanet:93571	Dense deposit disease

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
CFH	HGNC:4883	ENSG00000000971	P08603	Complement factor H	gencc
CFHR1	HGNC:4888	ENSG00000244414	Q03591	Complement factor H-related protein 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFH	Complement factor H	Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.
CFHR1	Complement factor H-related protein 1	Involved in complement regulation.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Complement	2	268.0×	1e-05

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFH	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFHR1	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med

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
calcaneal tendon	1
right coronary artery	1
urethra	1
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFH	267	ubiquitous	marker	urethra, calcaneal tendon, right coronary artery
CFHR1	125		marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFH	1,844
CFHR1	599

Intra-cohort edges

A	B	Sources
CFH	CFHR1	intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFH	P08603	51
CFHR1	Q03591	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Regulation of Complement cascade	2	233.1×	2e-05	CFH, CFHR1

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
complement activation	2	624.1×	2e-05	CFH, CFHR1
regulation of complement activation, alternative pathway	1	4213.0×	0.001	CFH
regulation of complement-dependent cytotoxicity	1	1685.2×	0.002	CFH
regulation of complement activation	1	1053.2×	0.002	CFH
obsolete cytolysis by host of symbiont cells	1	1053.2×	0.002	CFHR1
complement activation, alternative pathway	1	495.6×	0.003	CFH
central nervous system myelination	1	495.6×	0.003	CFH
negative regulation of protein binding	1	312.1×	0.004	CFHR1
inflammatory response	1	18.9×	0.058	CFH
proteolysis	1	17.1×	0.058	CFH

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFH	0	0
CFHR1	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
CFH	1	Binding:1

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	2	CFH, CFHR1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CFH	1	—
CFHR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 15.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	6
PHASE1	4
Not specified	3
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05809531	PHASE3	ACTIVE_NOT_RECRUITING	An Open-Label, Nonrandomized, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan in Participants With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
NCT05067127	PHASE3	COMPLETED	Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
NCT04183101	PHASE2	RECRUITING	Evaluation of a Renin Inhibitor, Aliskiren, Compared to Enalapril, in C3 Glomerulopathy
NCT03124368	PHASE2	COMPLETED	A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN
NCT03369236	PHASE2	COMPLETED	A Proof-of-Concept Study of Danicopan for 6 Months of Treatment in Participants With C3 Glomerulopathy (C3G)
NCT03453619	PHASE2	COMPLETED	Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies
NCT03459443	PHASE2	TERMINATED	A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471
NCT04572854	PHASE2	COMPLETED	Study Assessing the Safety and Efficacy of Pegcetacoplan in Post-Transplant Recurrence of C3G or IC-MPGN
NCT00583427	PHASE1	WITHDRAWN	Sulodexide Treatment in Patients With Dense Deposit Disease
NCT01221181	PHASE1	COMPLETED	Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy
NCT01791686	PHASE1	TERMINATED	Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease
NCT02302755	PHASE1	WITHDRAWN	TP10 Use in Patients With C3 Glomerulopathy (C3G)
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT03723512	Not specified	COMPLETED	Non-contrast Enhanced MRI in Patients With C3 Glomerulopathy (C3G) or Immune-complex Membranoproliferative Glomerulonephritis (IC-MPGN) Enrolled in the ACH471-205 Study
NCT04729062	Not specified	APPROVED_FOR_MARKETING	C3G/Primary IC-MPGN EAP

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEGCETACOPLAN	4	5
DANICOPAN	4	3
ENALAPRIL	4	3
ALISKIREN	4	1
ECULIZUMAB	4	1
SULODEXIDE	3	1
CDX-1135	1	1