Immunoglobulin-mediated membranoproliferative glomerulonephritis

Summary

Immunoglobulin-mediated membranoproliferative glomerulonephritis (MONDO:0014005) is a disease caused by DGKE (GenCC Strong), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include danicopan.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: DGKE (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 60
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunoglobulin-mediated membranoproliferative glomerulonephritis
Mondo ID	MONDO:0014005
OMIM	615008
Orphanet	329903
DOID	DOID:0080388
NCIT	C123055
UMLS	C3554330
MedGen	767244
GARD	0017506
Is cancer (heuristic)	no

Also known as: Ig-mediated membranoproliferative glomerulonephritis · Ig-mediated MPGN · immune complex mediated membranoproliferative glomerulonephritis · immunoglobulin-mediated membranoproliferative glomerulonephritis · immunoglobulin-mediated MPGN · membranoproliferative glomerulonephritis type I · mesangiocapillary glomerulonephritis type 1 · nephrotic syndrome, type 7 · nephrotic syndrome, type 7, with membranoproliferative glomerulonephritis · NPHS7

Data availability: 60 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › immunoglobulin-mediated membranoproliferative glomerulonephritis

Related subtypes (17): congenital nephrotic syndrome, Finnish type, nephrotic syndrome, type 4, LAMB2-related infantile-onset nephrotic syndrome, familial idiopathic steroid-resistant nephrotic syndrome, nephrotic syndrome, type 20, nephrotic syndrome, type 22, nephrotic syndrome, type 23, nephrotic syndrome, type 24, nephrotic syndrome, IIa 26, nephrotic syndrome, type 17, nephrotic syndrome, type 18, nephrotic syndrome, type 19, nephrotic syndrome, type 21, nephrotic syndrome 14, nephrotic syndrome 15, nephrotic syndrome 16, idiopathic multidrug-resistant nephrotic syndrome

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

60 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 12 pathogenic, 6 benign, 4 likely pathogenic, 3 conflicting classifications of pathogenicity, 3 benign/likely benign, 3 likely benign, 2 pathogenic/likely pathogenic, 1 pathogenic/pathogenic, low penetrance, 1 likely pathogenic/pathogenic, low penetrance, 1 pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179079	NM_003647.3(DGKE):c.62_65dup (p.Ile23fs)	DGKE	Pathogenic	criteria provided, single submitter
1322206	NM_003647.3(DGKE):c.1068_1071del (p.Asn356fs)	DGKE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
135640	NM_003647.3(DGKE):c.889-1G>A	DGKE	Pathogenic	criteria provided, multiple submitters, no conflicts
135641	NM_003647.3(DGKE):c.966G>A (p.Trp322Ter)	DGKE	Pathogenic	criteria provided, multiple submitters, no conflicts
1409980	NM_003647.3(DGKE):c.427C>T (p.Gln143Ter)	DGKE	Pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
3068304	NM_003647.3(DGKE):c.465-2A>G	DGKE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39578	NM_003647.3(DGKE):c.127C>T (p.Gln43Ter)	DGKE	Pathogenic	criteria provided, single submitter
39579	NM_003647.3(DGKE):c.610del (p.Thr204fs)	DGKE	Pathogenic	criteria provided, multiple submitters, no conflicts
39580	NM_003647.3(DGKE):c.889-2A>G	DGKE	Pathogenic	criteria provided, single submitter
397599	NM_003647.3(DGKE):c.1376G>A (p.Trp459Ter)	DGKE	Pathogenic	no assertion criteria provided
4278125	NM_003647.3(DGKE):c.389G>A (p.Gly130Asp)	DGKE	Pathogenic	criteria provided, single submitter
4292482	NM_003647.3(DGKE):c.142_143del (p.Gln48fs)	DGKE	Pathogenic	criteria provided, single submitter
4293294	NM_003647.3(DGKE):c.433_443del (p.Cys145fs)	DGKE	Pathogenic	criteria provided, single submitter
522493	NM_003647.3(DGKE):c.1009C>T (p.Arg337Ter)	DGKE	Pathogenic, low penetrance	criteria provided, single submitter
635454	NM_003647.3(DGKE):c.610dup (p.Thr204fs)	DGKE	Pathogenic	criteria provided, multiple submitters, no conflicts
829884	NM_003647.3(DGKE):c.1099-2A>T	DGKE	Pathogenic	no assertion criteria provided
1329494	NM_003647.3(DGKE):c.842G>A (p.Gly281Glu)	DGKE	Likely pathogenic	criteria provided, single submitter
397600	NM_003647.3(DGKE):c.1169G>A (p.Arg390His)	DGKE	Likely pathogenic	no assertion criteria provided
424621	NM_003647.3(DGKE):c.728_731del (p.Ile242_Leu243insTer)	DGKE	Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
522494	NM_003647.3(DGKE):c.178C>G (p.His60Asp)	DGKE	Likely pathogenic	no assertion criteria provided
635453	NM_003647.3(DGKE):c.1442dup (p.Val482fs)	DGKE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163611	NM_003647.3(DGKE):c.259T>C (p.Cys87Arg)	DGKE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289334	NM_003647.3(DGKE):c.1679A>G (p.Gln560Arg)	DGKE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290120	NM_003647.3(DGKE):c.35C>T (p.Pro12Leu)	DGKE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032142	NM_003647.3(DGKE):c.303G>C (p.Lys101Asn)	DGKE	Uncertain significance	criteria provided, multiple submitters, no conflicts
1032143	NM_003647.3(DGKE):c.995T>C (p.Val332Ala)	DGKE	Uncertain significance	criteria provided, multiple submitters, no conflicts
1297633	NM_003647.3(DGKE):c.851G>A (p.Gly284Glu)	DGKE	Uncertain significance	criteria provided, single submitter
1312987	NM_003647.3(DGKE):c.713G>A (p.Gly238Glu)	DGKE	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339010	NM_003647.3(DGKE):c.293G>A (p.Cys98Tyr)	DGKE	Uncertain significance	criteria provided, single submitter
1347716	NM_003647.3(DGKE):c.1688T>C (p.Ile563Thr)	DGKE	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
DGKE	Strong	Autosomal recessive	immunoglobulin-mediated membranoproliferative glomerulonephritis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DGKE	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
DGKE	Orphanet:357008	Hemolytic uremic syndrome with DGKE deficiency

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
DGKE	HGNC:2852	ENSG00000153933	P52429	Diacylglycerol kinase epsilon	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DGKE	Diacylglycerol kinase epsilon	Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

Protein-family classification

Druggable: 1 · 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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DGKE	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, PKC_DAG/PE

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
Brodmann (1909) area 23	1
buccal mucosa cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DGKE	250	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DGKE	1,045

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DGKE	P52429	86.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Effects of PIP2 hydrolysis	1	456.8×	0.002	DGKE

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
glycerolipid metabolic process	1	2106.5×	0.002	DGKE
lipid phosphorylation	1	1685.2×	0.002	DGKE
diacylglycerol metabolic process	1	1203.7×	0.002	DGKE
phosphatidic acid biosynthetic process	1	510.7×	0.004	DGKE
phosphatidylinositol biosynthetic process	1	366.4×	0.005	DGKE
platelet activation	1	267.5×	0.006	DGKE
modulation of chemical synaptic transmission	1	183.2×	0.007	DGKE
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.009	DGKE
intracellular signal transduction	1	38.1×	0.026	DGKE

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
DGKE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DGKE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DGKE	2.7.1.107	diacylglycerol kinase (ATP)

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	1	DGKE
E	Difficult family or no structure, no drug	0

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)
DGKE	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03124368	PHASE2	COMPLETED	A Proof-of-Mechanism Study to Determine the Effect of Danicopan on C3 Levels in Participants With C3G or IC-MPGN

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DANICOPAN	4	1