◎ Sugi Atlas

Atlas / Disease / Membranous glomerulonephritis

Membranous glomerulonephritis

disease
On this page

Also known as membranous Glomerulonephropathymembranous nephropathy

Summary

Membranous glomerulonephritis (MONDO:0005376) is a disease with 17 cohort genes (34 GWAS associations across 5 studies) and 68 clinical trials. Top therapeutic interventions include rituximab, obinutuzumab, and belimumab.

At a glance

  • Cohort genes: 17
  • GWAS associations: 34
  • Clinical trials: 68

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namemembranous glomerulonephritis
Mondo IDMONDO:0005376
EFOEFO:0004254
MeSHD015433
DOIDDOID:10976
NCITC34645
SNOMED CT77182004
UMLSC0017665
MedGen42231
GARD0024178
Anatomy (UBERON)UBERON:0005777
Is cancer (heuristic)no

Also known as: membranous Glomerulonephropathy · membranous nephropathy

Data availability: 34 GWAS associations (5 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › nephritis › glomerulonephritis › membranous 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, lupus nephritis, minimal change disease, granulomatosis with polyangiitis, rapidly progressive glomerulonephritis, primary membranoproliferative glomerulonephritis, Pauci-immune glomerulonephritis, immunotactoid glomerulopathy, autoimmune glomerulonephritis

Subtypes (1): idiopathic membranous glomerulonephritis

Genetics & variants

GWAS landscape

34 GWAS associations across 5 studies. Top hits map to 20 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs92715733e-154HLA-DRB1 - HLA-DQA1A2.41
rs178312515e-103PLA2R1C2.25
rs21876688e-93HLA-DQA1A4.32
rs31347926e-72LINC02571 - HLA-BC3.93
rs77753975e-71TSBP1-AS1, TSBP1G3.83
rs3898848e-66WHR1C3.65
rs2305402e-61NFKB1C1.24
rs77506413e-58TCF19T3.35
rs31305449e-58RNU6-1133P - C6orf15A3.34
rs31156637e-57PRRC2AG3.04
rs92675221e-56PRRC2AG3.04
rs31306182e-56GPANK1A3.03
rs19804931e-48BTNL2, TSBP1-AS1G2.87
rs22339566e-48C6orf15 - PSORS1C1G2.77
rs6528883e-46EHMT2-AS1, EHMT2C2.71
rs31305641e-42PSORS1C1T2.62
rs30966971e-41EGFL8, PPT2-EGFL8T2.58
rs31349452e-40RNF5T2.54
rs31299392e-40TSBP1-AS1, TSBP1G2.6
rs31325803e-40MUCL3, SFTA2, HCG21T2.74
rs2049999e-40FKBPL - PPT2G2.44
rs92727292e-39HLA-DQA1A7.07
rs14803804e-39HLA-DMB - HLA-DMAT3.05
rs12651594e-37POU5F1T2.42
rs46643089e-29PLA2R1A2.28
rs94051921e-14DUSP22 - IRF4G1.29
rs178305584e-10PLA2R1T1.87

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST010004Xie J20202,1505,829The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.
GCST010005Xie J20202,1505,829The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.
GCST010006Xie J20201,6121,970The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.
GCST000984Stanescu HC20115562,338Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.
GCST003402Sekula P20163230Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding6
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic20

MAF distribution

BucketVariants
common (>=0.05)27
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant16
missense_variant5
intergenic_variant3
regulatory_region_variant1
non_coding_transcript_exon_variant1
stop_gained1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs9271573632622724A>C0.05regulatory_region_variantHLA-DRB1 - HLA-DQA13e-154Tier 3: regulatory
rs178312512160057645C>T0.05intron_variantPLA2R15e-103Tier 4: intronic/intergenic
rs2187668632638107C>A,G,T0.13intron_variantHLA-DQA18e-93Tier 4: intronic/intergenic
rs3134792631344549T>G0.114intron_variantLINC02571 - HLA-B6e-72Tier 4: intronic/intergenic
rs7775397632293475T>G0.114missense_variantTSBP1-AS1, TSBP15e-71Tier 1: coding
rs389884631973120A>G,T0.115intron_variantWHR18e-66Tier 4: intronic/intergenic
rs2305404102575510C>A,G,T0.35intron_variantNFKB12e-61Tier 4: intronic/intergenic
rs7750641631161533C>T0.126missense_variantTCF193e-58Tier 1: coding
rs3130544631090563C>A0.124intergenic_variantRNU6-1133P - C6orf159e-58Tier 4: intronic/intergenic
rs3115663631634066T>A,C,G0.181intron_variantPRRC2A7e-57Tier 4: intronic/intergenic
rs92675226316359930.181missense_variantPRRC2A1e-56Tier 1: coding
rs3130618631664357C>A,G,T0.181missense_variantGPANK12e-56Tier 1: coding
rs1980493632395438T>A,C,G0.166intron_variantBTNL2, TSBP1-AS11e-48Tier 4: intronic/intergenic
rs2233956631113428T>A,C,G0.181intergenic_variantC6orf15 - PSORS1C16e-48Tier 4: intronic/intergenic
rs652888631883457A>C,G,T0.202non_coding_transcript_exon_variantEHMT2-AS1, EHMT23e-46Tier 4: intronic/intergenic
rs3130564631133897C>T0.193intron_variantPSORS1C11e-42Tier 4: intronic/intergenic
rs3096697632166733G>A,C,T0.205missense_variantEGFL8, PPT2-EGFL81e-41Tier 1: coding
rs3134945632178715C>A,G,T0.205intron_variantRNF52e-40Tier 4: intronic/intergenic
rs3129939632368989A>G0.177intron_variantTSBP1-AS1, TSBP12e-40Tier 4: intronic/intergenic
rs3132580630952347G>A,C,T0.138stop_gainedMUCL3, SFTA2, HCG213e-40Tier 1: coding
rs204999632142202A>G0.264intergenic_variantFKBPL - PPT29e-40Tier 4: intronic/intergenic
rs9272729632641817G>A,C,T0.2intron_variantHLA-DQA12e-39Tier 4: intronic/intergenic
rs1480380632945469C>T0.088intron_variantHLA-DMB - HLA-DMA4e-39Tier 4: intronic/intergenic
rs1265159631172270G>A,C,T0.219intron_variantPOU5F14e-37Tier 4: intronic/intergenic
rs46643082160060986A>G0.43intron_variantPLA2R19e-29Tier 4: intronic/intergenic
rs94051926382537G>A,C,T0.05intron_variantDUSP22 - IRF41e-14Tier 4: intronic/intergenic
rs178305582160021853T>A,G0.48intron_variantPLA2R14e-10Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BTNL2Orphanet:797Sarcoidosis
MUCL3Orphanet:171700Diffuse panbronchiolitis
HLA-DQA1Orphanet:391490Adult-onset myasthenia gravis
HLA-DQA1Orphanet:930Idiopathic achalasia
IRF4Orphanet:3452Whipple disease
ITGB6Orphanet:100031Hypoplastic amelogenesis imperfecta
ITGB6Orphanet:100032Hypocalcified amelogenesis imperfecta
ITGB6Orphanet:2850Alopecia-intellectual disability syndrome
NFKB1Orphanet:696874NFKB1-related immune dysregulation

Cohort genes → proteins

17 cohort genes, 17 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only17

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RNF5HGNC:10068ENSG00000204308Q99942E3 ubiquitin-protein ligase RNF5gwas
BTNL2HGNC:1142ENSG00000204290Q9UIR0Butyrophilin-like protein 2gwas
TCF19HGNC:11629ENSG00000137310Q9Y242Transcription factor 19gwas
PRRC2AHGNC:13918ENSG00000204469P48634Protein PRRC2Agwas
GPANK1HGNC:13920ENSG00000204438O95872G patch domain and ankyrin repeat-containing protein 1gwas
TSBP1HGNC:13922ENSG00000204296Q5SRN2Testis-expressed basic protein 1gwas
EGFL8HGNC:13944ENSG00000241404Q99944Epidermal growth factor-like protein 8gwas
EHMT2HGNC:14129ENSG00000204371Q96KQ7Histone-lysine N-methyltransferase EHMT2gwas
PSORS1C1HGNC:17202ENSG00000204540Q9UIG5Psoriasis susceptibility 1 candidate gene 1 proteingwas
MUCL3HGNC:21666ENSG00000168631Q3MIW9Mucin-like protein 3gwas
HLA-DQA1HGNC:4942ENSG00000196735P01909HLA class II histocompatibility antigen, DQ alpha 1 chaingwas
IRF4HGNC:6119ENSG00000137265Q15306Interferon regulatory factor 4gwas
ITGB6HGNC:6161ENSG00000115221P18564Integrin beta-6gwas
LY75HGNC:6729ENSG00000054219O60449Lymphocyte antigen 75gwas
NFKB1HGNC:7794ENSG00000109320P19838Nuclear factor NF-kappa-B p105 subunitgwas
PLA2R1HGNC:9042ENSG00000153246Q13018Secretory phospholipase A2 receptorgwas
RBMS1HGNC:9907ENSG00000153250P29558RNA-binding motif, single-stranded-interacting protein 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RNF5E3 ubiquitin-protein ligase RNF5Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins.
BTNL2Butyrophilin-like protein 2Negative regulator of T-cell proliferation.
TCF19Transcription factor 19Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition.
PRRC2AProtein PRRC2AMay play a role in the regulation of pre-mRNA splicing.
EHMT2Histone-lysine N-methyltransferase EHMT2Histone methyltransferase that specifically mono- and dimethylates ‘Lys-9’ of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin.
MUCL3Mucin-like protein 3May modulate NF-kappaB signaling and play a role in cell growth.
HLA-DQA1HLA class II histocompatibility antigen, DQ alpha 1 chainBinds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
IRF4Interferon regulatory factor 4Transcriptional activator.
ITGB6Integrin beta-6Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for fibronectin and cytotactin.
LY75Lymphocyte antigen 75Acts as an endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment.
NFKB1Nuclear factor NF-kappa-B p105 subunitNF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as infl…
PLA2R1Secretory phospholipase A2 receptorReceptor for secretory phospholipase A2 (sPLA2).
RBMS1RNA-binding motif, single-stranded-interacting protein 1Single-stranded DNA binding protein that interacts with the region upstream of the MYC gene.

Protein-family classification

Druggable: 2 · Difficult: 5 · Unknown: 10 · Druggable fraction: 0.12

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.

FamilyGenesFoldFDR
Antibody/Immunoglobulin23.4×0.453
Scaffold/PPI22.0×0.453
Transcription factor31.5×0.453
Other/Unknown101.1×0.502

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RNF5Transcription factornoZnf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
BTNL2Antibody/ImmunoglobulinyesIg_C1-set, Ig_sub, Ig-like_dom
TCF19Transcription factornoFHA_dom, Znf_PHD, SMAD_FHA_dom_sf
PRRC2AOther/UnknownnoBAT2_N, PRRC2
GPANK1Scaffold/PPInoG_patch_dom, Ankyrin_rpt, Ankyrin_rpt-contain_sf
TSBP1Other/UnknownnoTSBP1
EGFL8Other/UnknownnoEGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
EHMT2Scaffold/PPIno2.1.1.355SET_dom, Ankyrin_rpt, Pre-SET_dom
PSORS1C1Other/UnknownnoSEEK1
MUCL3Other/UnknownnoMUCL3
HLA-DQA1Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
IRF4Other/UnknownnoInterferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
ITGB6Other/UnknownnoIntegrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell
LY75Other/UnknownnoFN_type2_dom, Ricin_B_lectin, C-type_lectin-like
NFKB1Transcription factornoNFkB/Dor, Death_dom, Ankyrin_rpt
PLA2R1Other/UnknownnoFN_type2_dom, Ricin_B_lectin, C-type_lectin-like
RBMS1Other/UnknownnoRRM_dom, Hud_Sxl_RNA, Nucleotide-bd_a/b_plait_sf

Expression context

Cohort genes with no expression data: 0.

13 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)17
unknown0

Top tissues across cohort

TissueCohort genes
left testis4
right testis4
ventricular zone3
testis3
ganglionic eminence2
primordial germ cell in gonad2
sural nerve2
lymph node2
lower esophagus mucosa2
adult mammalian kidney1
cortical plate1
tibial nerve1
nucleus accumbens1
putamen1
body of stomach1
mucosa of stomach1
gall bladder1
monocyte1
rectum1
endocervix1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RNF5134ubiquitousmarkerganglionic eminence, adult mammalian kidney, cortical plate
BTNL2106yessural nerve, ventricular zone, primordial germ cell in gonad
TCF19133ubiquitousyesprimordial germ cell in gonad, ventricular zone, lymph node
PRRC2A134ubiquitousmarkerright testis, left testis, ventricular zone
GPANK1133ubiquitousmarkerleft testis, right testis, testis
TSBP158tissue_specificyesleft testis, testis, right testis
EGFL8133broadmarkertibial nerve, lower esophagus mucosa, sural nerve
EHMT2134ubiquitousmarkernucleus accumbens, ganglionic eminence, putamen
PSORS1C1124ubiquitousyesleft testis, right testis, testis
MUCL351tissue_specificmarkermucosa of stomach, lower esophagus mucosa, body of stomach
HLA-DQA1244broadmarkergall bladder, rectum, monocyte
IRF4180broadmarkerlymph node, endocervix, vermiform appendix
ITGB6188broadmarkervisceral pleura, biceps brachii, skeletal muscle tissue of rectus abdominis
LY75242broadmarkerthymus, epithelium of nasopharynx, jejunal mucosa
NFKB1252ubiquitousmarkerendometrium epithelium, cartilage tissue, calcaneal tendon
PLA2R1233ubiquitousmarkerparotid gland, left lobe of thyroid gland, thyroid gland
RBMS1264ubiquitousmarkercauda epididymis, oviduct epithelium, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

SymbolInteractor count
NFKB110,484
EHMT24,723
IRF43,450
PRRC2A2,550
TCF191,774
RNF51,666
ITGB61,461
LY751,283
RBMS11,265
BTNL2998

Intra-cohort edges

ABSources
BTNL2TSBP1string_interaction
EHMT2TCF19string_interaction
GPANK1PRRC2Astring_interaction
ITGB6RBMS1string_interaction
PSORS1C1TCF19string_interaction
PSORS1C1TSBP1string_interaction
RNF5TSBP1string_interaction

Structural data

PDB: 8 · AlphaFold-only: 9 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
EHMT2Q96KQ735
HLA-DQA1P0190928
IRF4Q1530619
NFKB1P1983815
ITGB6P1856414
LY75O604494
RBMS1P295583
PLA2R1Q130182

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
BTNL2Q9UIR085.97
EGFL8Q9994476.30
GPANK1O9587271.48
RNF5Q9994268.71
TCF19Q9Y24263.17
PSORS1C1Q9UIG555.10
MUCL3Q3MIW947.09
TSBP1Q5SRN245.58
PRRC2AP4863440.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 86. Enrichment computed across 17 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Transcriptional Regulation by VENTX259.0×0.042EHMT2, NFKB1
PKMTs methylate histone lysines235.7×0.047EHMT2, NFKB1
Downstream TCR signaling228.5×0.047HLA-DQA1, NFKB1
Interferon gamma signaling227.9×0.047HLA-DQA1, IRF4
CLEC7A/inflammasome pathway1211.5×0.057NFKB1
DEx/H-box helicases activate type I IFN and inflammatory cytokines production1181.3×0.057NFKB1
IkBA variant leads to EDA-ID1181.3×0.057NFKB1
Regulation of NFE2L2 gene expression1158.6×0.057NFKB1
Interleukin-1 processing1141.0×0.057NFKB1
Regulated proteolysis of p75NTR1115.3×0.057NFKB1
NF-kB is activated and signals survival197.6×0.057NFKB1
Butyrophilin (BTN) family interactions197.6×0.057BTNL2
MAP3K8 (TPL2)-dependent MAPK1/3 activation179.3×0.057NFKB1
Calnexin/calreticulin cycle179.3×0.057RNF5
Acyl chain remodelling of PI174.6×0.057PLA2R1
RIP-mediated NFkB activation via ZBP1174.6×0.057NFKB1
The NLRP3 inflammasome174.6×0.057NFKB1
Acyl chain remodelling of PG170.5×0.057PLA2R1
Translocation of ZAP-70 to Immunological synapse170.5×0.057HLA-DQA1
Phosphorylation of CD3 and TCR zeta chains160.4×0.057HLA-DQA1
Regulation of TP53 Activity through Methylation160.4×0.057EHMT2
ER Quality Control Compartment (ERQC)160.4×0.057RNF5
Acyl chain remodelling of PS157.7×0.057PLA2R1
Co-inhibition by PD-1157.7×0.057HLA-DQA1
CD209 (DC-SIGN) signaling157.7×0.057NFKB1
Senescence-Associated Secretory Phenotype (SASP)222.1×0.057EHMT2, NFKB1
TRAF6 mediated NF-kB activation150.8×0.058NFKB1
ABC transporter disorders148.8×0.058RNF5
Acyl chain remodelling of PC147.0×0.058PLA2R1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle147.0×0.058RNF5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
phenotypic switching11296.3×0.030EHMT2
negative regulation of arachidonate secretion11296.3×0.030PLA2R1
transforming growth factor beta production1648.1×0.030ITGB6
positive regulation of podocyte apoptotic process1648.1×0.030PLA2R1
memory T cell differentiation1432.1×0.030ITGB6
positive regulation of miRNA metabolic process1432.1×0.030NFKB1
negative regulation of vitamin D biosynthetic process1324.1×0.030NFKB1
regulation of T-helper cell differentiation1324.1×0.030IRF4
Langerhans cell differentiation1324.1×0.030ITGB6
oxidative stress-induced premature senescence1324.1×0.030PLA2R1
positive regulation of hyaluronan biosynthetic process1324.1×0.030NFKB1
peptidyl-lysine dimethylation1259.3×0.030EHMT2
bronchiole development1259.3×0.030ITGB6
cellular response to dsRNA1259.3×0.030NFKB1
positive regulation of arachidonate secretion1259.3×0.030PLA2R1
positive regulation of interleukin-2 production272.0×0.030BTNL2, IRF4
inflammatory response38.7×0.032ITGB6, LY75, NFKB1
mammary gland involution1216.1×0.032NFKB1
cellular response to interleukin-171185.2×0.035NFKB1
cellular response to nicotine1162.0×0.038NFKB1
hard palate development1129.6×0.042ITGB6
T-helper 17 cell lineage commitment1117.8×0.042IRF4
antibacterial innate immune response1117.8×0.042NFKB1
positive regulation of lipid storage1108.0×0.042NFKB1
amelogenesis1108.0×0.042ITGB6
cellular response to cocaine199.7×0.042EHMT2
negative regulation of autophagosome assembly199.7×0.042EHMT2
enamel mineralization192.6×0.042ITGB6
endoplasmic reticulum mannose trimming192.6×0.042RNF5
positive regulation of interleukin-13 production186.4×0.042IRF4

Therapeutics

Drugs indicated for this disease

0 approved, 8 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
ChlorambucilPhase 3 (in late-stage trials)
CyclosporinePhase 3 (in late-stage trials)
MethylprednisolonePhase 3 (in late-stage trials)
Mycophenolate MofetilPhase 3 (in late-stage trials)
PrednisolonePhase 3 (in late-stage trials)
PrednisonePhase 3 (in late-stage trials)
RituximabPhase 3 (in late-stage trials)
Tacrolimus AnhydrousPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Belimumab, Cosyntropin, Iptacopan.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 14

Druggability breadth: 9 of 17 evidence-associated genes (53%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
EHMT2RALTITREXED
NFKB1INDOPROFEN

Top cohort targets by molecule count

SymbolMoleculesMax phase
NFKB11524
EHMT274
ITGB653
RNF500
BTNL200
TCF1900
PRRC2A00
GPANK100
TSBP100
EGFL800

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
RALTITREXED4EHMT2
TAZEMETOSTAT4EHMT2
DISULFIRAM4EHMT2, NFKB1
INDOPROFEN4NFKB1
VAMOROLONE4NFKB1
BORTEZOMIB4NFKB1
DEXAMETHASONE4NFKB1
SULFASALAZINE4NFKB1
LEVOSALBUTAMOL4NFKB1
CLOTRIMAZOLE4NFKB1
GLIPIZIDE4NFKB1
SALMETEROL XINAFOATE4NFKB1
PHENELZINE4NFKB1
SULFAPHENAZOLE4NFKB1
AMOXAPINE4NFKB1
PROPANTHELINE4NFKB1
DECAMETHONIUM4NFKB1
NICARDIPINE HYDROCHLORIDE4NFKB1
PHENTOLAMINE MESYLATE4NFKB1
PHENYLEPHRINE4NFKB1
CARISOPRODOL4NFKB1
AZELAIC ACID4NFKB1
CARBETAPENTANE CITRATE4NFKB1
NIALAMIDE4NFKB1
EPINEPHRINE BITARTRATE4NFKB1
NILUTAMIDE4NFKB1
BUDESONIDE4NFKB1
ESTRONE4NFKB1
METHAPYRILENE4NFKB1
PIMOZIDE4NFKB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
EHMT2442Binding:435, Functional:6, ADMET:1
NFKB1256Binding:249, Functional:7
ITGB679Binding:75, ADMET:2, Functional:2
IRF43Binding:3
PLA2R13Binding:3
RNF52Binding:2
HLA-DQA12Binding:2
PRRC2A1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
EHMT22.1.1.355, 2.1.1.356, 2.1.1.367, 2.1.1.368[histone H3]-lysine9 N-trimethyltransferase, [histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine9 N-dimethyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
EHMT2442
NFKB1256

Pharmacogenomics

Cohort genes with a PharmGKB record: 17; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

CompoundMax phaseCohort target (bioactivity)
RALTITREXED4EHMT2
TAZEMETOSTAT4EHMT2
DISULFIRAM4EHMT2, NFKB1
INDOPROFEN4NFKB1
VAMOROLONE4NFKB1
BORTEZOMIB4NFKB1
DEXAMETHASONE4NFKB1
SULFASALAZINE4NFKB1
LEVOSALBUTAMOL4NFKB1
CLOTRIMAZOLE4NFKB1
GLIPIZIDE4NFKB1
SALMETEROL XINAFOATE4NFKB1
PHENELZINE4NFKB1
SULFAPHENAZOLE4NFKB1
AMOXAPINE4NFKB1
PROPANTHELINE4NFKB1
DECAMETHONIUM4NFKB1
NICARDIPINE HYDROCHLORIDE4NFKB1
PHENTOLAMINE MESYLATE4NFKB1
PHENYLEPHRINE4NFKB1
CARISOPRODOL4NFKB1
AZELAIC ACID4NFKB1
CARBETAPENTANE CITRATE4NFKB1
NIALAMIDE4NFKB1
EPINEPHRINE BITARTRATE4NFKB1
NILUTAMIDE4NFKB1
BUDESONIDE4NFKB1
ESTRONE4NFKB1
METHAPYRILENE4NFKB1
PIMOZIDE4NFKB1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2EHMT2, NFKB1
BPhased (≥1) drug, not yet approved1ITGB6
CDruggable family + PDB, no drug1HLA-DQA1
DDruggable family + AlphaFold only, no drug1BTNL2
EDifficult family or no structure, no drug12RNF5, TCF19, PRRC2A, GPANK1, TSBP1, EGFL8, PSORS1C1, MUCL3, IRF4, LY75 (+2 more)

Undrugged target profiles

14 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
RBMS10ITGB6
RNF52—
BTNL20—
TCF190—
PRRC2A1—
GPANK10—
TSBP10—
EGFL80—
PSORS1C10—
MUCL30—
HLA-DQA12—
IRF43—
LY750—
PLA2R13—

Clinical trials & evidence

Clinical trials

Clinical trials: 68.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE220
Not specified18
PHASE38
PHASE16
PHASE44
PHASE2/PHASE34
PHASE1/PHASE24
EARLY_PHASE14

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05514015PHASE4RECRUITINGClinical Study of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in the Treatment of Primary Membranous Nephropathy
NCT06573411PHASE4RECRUITINGEfficacy and Safety of Finerenone in Patients With Primary Membranous Nephropathy
NCT00518219PHASE4COMPLETEDTo Compare the Efficacy and Safety of Tripterygium Wilfordii (TW) Versus Valsartan in the Membranous Nephropathy (MN)
NCT03025828PHASE4COMPLETEDAdrenocorticotropic Hormone in Membranous Nephropathy
NCT04629248PHASE3ACTIVE_NOT_RECRUITINGA Study Evaluating the Efficacy and Safety of Obinutuzumab in Participants With Primary Membranous Nephropathy
NCT05707377PHASE2/PHASE3ACTIVE_NOT_RECRUITINGA Study to Examine the Efficacy and Safety of Zanubrutinib Given to Adults With Primary Membranous Nephropathy
NCT05862233PHASE3ACTIVE_NOT_RECRUITINGA Phase Ⅲ Clinical Study of MIL62 in Primary Membranous Nephropathy
NCT06341205PHASE3RECRUITINGPersonalized Rituximab Treatment Based on Artificial Intelligence in Membranous Nephropathy (iRITUX)
NCT06470191PHASE2/PHASE3RECRUITINGA Clinical Study of B007 in the Treatment of Primary Membranous Nephropathy.
NCT06781944PHASE3RECRUITINGOBINOTUZUMAB Versus Cyclophosphamide + Glucocorticoids in Primary Membranous Nephropathy(Blossom Study)
NCT06962800PHASE3RECRUITINGA Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Primary Membranous Nephropathy (PMN)
NCT07204275PHASE2/PHASE3RECRUITINGEvaluation of Efficacy, Safety, and Tolerability of Povetacicept in Participants With Primary Membranous Nephropathy (pMN)
NCT00425217PHASE2/PHASE3COMPLETEDRituximab in Membranous Nephropathy
NCT01955187PHASE3COMPLETEDSequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy
NCT05696613PHASE3UNKNOWNA Study of SNP-ACTH (1-39) Gel in Patients With Primary Membranous Nephropathy
NCT06120673PHASE3WITHDRAWNREmission in Membranous Nephropathy International Trial (REMIT)
NCT00977977PHASE2RECRUITINGRituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT03949855PHASE2RECRUITINGBelimumab With Rituximab for Primary Membranous Nephropathy
NCT05050214PHASE2ACTIVE_NOT_RECRUITINGObinutuzumab in Primary MN
NCT05732402PHASE1/PHASE2ACTIVE_NOT_RECRUITINGAn Open-label Study of Povetacicept in Autoantibody-Associated Glomerular Diseases
NCT06466135PHASE2RECRUITINGStudy of WAL0921 in Patients With Glomerular Kidney Diseases
NCT06557265PHASE1/PHASE2RECRUITINGA Phase 1/2 Study of NKX019 in Subjects With Autoimmune Disease (Ntrust-1)
NCT06614985PHASE2NOT_YET_RECRUITINGThe Efficacy and Safety of Treatment With Telitacicept in Primary Membranous Nephropathy
NCT06642909PHASE2ACTIVE_NOT_RECRUITINGA Phase II Study of Zuberitamab Injection in Patients With Primary Membranous Nephropathy
NCT07029139PHASE2NOT_YET_RECRUITINGA Study to Learn More About the Effects and Safety of JMT601 in Adults With Primary Membranous Nephropathy
NCT07038382PHASE2RECRUITINGA Study to Evaluate the Efficacy, Safety, and Tolerability of Human Sialidase Fusion Protein (HLX79) in Combination With Rituximab Injection Versus Placebo in Patients With Active Glomerulonephritis
NCT07096843PHASE2RECRUITINGA Phase 2 Study of Budoprutug in Subjects With Primary Membranous Nephropathy
NCT07157787PHASE2RECRUITINGStudy of ALXN1920 in Adult Participants With Primary Membranous Nephropathy (PMN)
NCT07289763PHASE2RECRUITINGPhase II Randomized, Open-label, Multicenter Clinical Study Evaluating the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of SHR-2173 Injection in Patients With Primary Membranous Nephropathy
NCT07571746PHASE2RECRUITINGA Study to Assess the Effect of Surovatamig in Adult Participants With Antibody-mediated Kidney Disease
NCT00050713PHASE2COMPLETEDSirolimus Therapy for Idiopathic and Lupus Membranous Nephropathy
NCT03453619PHASE2COMPLETEDPhase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies
NCT04652570PHASE1/PHASE2TERMINATEDEfficacy and Safety of VB119 in Subjects With Membranous Nephropathy
NCT04733040PHASE2COMPLETEDEfficacy, Safety and PK/PD of MOR202 in Anti-PLA2R+ Membranous Nephropathy (aMN) (NewPLACE)
NCT04893096PHASE2COMPLETEDMOR202 for Refractory MN
NCT05136456PHASE2UNKNOWNEvaluate the Efficacy and Safety of SHR1459 Tablets in Patients With Primary Membranous Nephropathy
NCT05162066PHASE2TERMINATEDStudy to Evaluate the Safety, Tolerability of BCX9930 in Participants With Either Complement 3 Glomerulopathy (C3G), Immunoglobulin A Nephropathy (IgAN), or Primary Membranous Nephropathy (PMN)
NCT05398653PHASE1/PHASE2COMPLETEDA Phase Ib/ Ⅱ Clinical Study of MIL62 in Primary Membranous Nephropathy
NCT05810961PHASE2TERMINATEDA Study to Assess Effectiveness and Safety of Efgartigimod in Chinese Patients with Primary Membranous Nephropathy (ZL-1103-014)
NCT05941845PHASE2UNKNOWNInterferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
RITUXIMAB410
OBINUTUZUMAB43
BELIMUMAB41
CORTICOTROPIN41
DIPHENHYDRAMINE41
PEGCETACOPLAN41
ZANUBRUTINIB41
FELZARTAMAB33
TELITACICEPT31
BUDOPRUTUG22
POVETACICEPT22
SUROVATAMIG21
CHEMBL519312801

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 73

This page pulls from 73 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot