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Atlas / Disease / Monoclonal gammopathy

Monoclonal gammopathy

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Summary

Monoclonal gammopathy (MONDO:0004960) is a disease with 19 cohort genes (80 GWAS associations across 10 studies) and 14 clinical trials. Top therapeutic interventions include daratumumab, isatuximab, and liraglutide.

At a glance

  • Cohort genes: 19
  • GWAS associations: 80
  • Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namemonoclonal gammopathy
Mondo IDMONDO:0004960
EFOEFO:0000203
MeSHD010265
ICD-10-CMD47.2
NCITC35548
SNOMED CT109983007
UMLSC1136085
MedGen210153
GARD0024137
Is cancer (heuristic)no

Data availability: 80 GWAS associations (10 studies).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › monoclonal gammopathy

Related subtypes (26): autoimmune disorder of blood, blood coagulation disease, hemorrhagic disease, blood platelet disease, anemia, splenic disorder, hematopoietic and lymphoid system neoplasm, blood group incompatibility, bone marrow disorder, thymus gland disorder, leukocyte disorder, septicemic plague, hyperamylasemia, alpha thalassemia-intellectual disability syndrome type 1, Bloom syndrome, congenital hematological disorder, alpha-thalassemia-myelodysplastic syndrome, deafness-lymphedema-leukemia syndrome, L-ferritin deficiency, dyskeratosis congenita, autosomal dominant 6, polyclonal hyperviscosity syndrome, parasitemia, erythrocyte disorder, premalignant hematological system disease, GATA1-Related X-Linked Cytopenia, paraneoplastic hematological syndrome

Subtypes (3): monoclonal paraproteinemia disease, monoclonal gammopathy of uncertain significance, acquired monoclonal Ig light chain-associated Fanconi syndrome

Genetics & variants

GWAS landscape

80 GWAS associations across 10 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs42730772e-19TNFRSF13B?1.24
rs67815291e-15ULK4T1.2
rs75775998e-15DTNB?0.86
rs5440951304e-14ELL2?0.87
rs17169811e-13ULK4?0.87
rs1151168562e-13EXOC2C2.14
rs98112162e-12ACTRT3 - MYNN?0.88
rs110850157e-12NFIC?0.87
rs1953144e-11TPTEP2, TPTEP2-CSNK1EG0.3
rs101180407e-11DELEC1, TNC x CRYL1C2.64
rs129592137e-11SETBP1 - SLC14A2 x PREX1T2.39
rs15467179e-11ERBB4 x RORAA5.03
rs64557441e-10PRKN x RN7SL714P - LINC02914C2.92
rs24671121e-10LINC02955 x TMC2T3.24
rs6741351e-10RPL5P6 - HFM1 x LINC01075 - LINC01074A2.61
rs562190662e-10ELL2T1.24
rs579684583e-10COTL1P1 - TBC1D27PA0.33
rs14379193e-10CPS1 - RPS27P10 x PTPRDG3.38
rs10117803e-10AUTS2 x HS6ST3G2.4
rs26195663e-10CNTN4 x TAFA1A4.66
rs2002038253e-10SOHLH2, CCDC169-SOHLH2AC1.39
rs17001124e-10CSMD1 x HMGB3P23 - RNA5SP281A2.16
rs49094944e-10KHDRBS3 x KSR2T2.51
rs8080345e-10FAM184A x FRMD4AC0.46
rs78677715e-10LINC03041 x CDH13C2.2
rs50121275e-10ATP6V1G1P7 - RPL7P45 x ISCA1P3 - ARL2BPP8A2.81
rs69199086e-10USP8P1T0.23
rs747404266e-10CDCA7 - JPT1P1?1.2
rs37474814e-09PRR14?1.11
rs21881276e-09CDKN2A-AS1?0.87

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90624746Guler M20259,6091,223,020Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST90624745Guler M20255,1061,223,020Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST012397Duran-Lozano L20214,376422,293Germline variants at SOHLH2 influence multiple myeloma risk.
GCST002922Swaminathan B20152,194294,390Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.
GCST90129580Clay-Gilmour A20221,7383,755Genome-wide meta-analysis of monoclonal gammopathy of undetermined significance (MGUS) identifies risk loci impacting IRF-6.
GCST007824Thomsen H20199922,910Genome-wide association study of monoclonal gammopathy of unknown significance (MGUS): comparison with multiple myeloma.
GCST010507Clay-Gilmour AI20207540Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance.
GCST006917Chattopadhyay S20182431,285Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance: a genome-wide genetic interaction study.
GCST004287Thomsen H2017243243Genomewide association study on monoclonal gammopathy of unknown significance (MGUS).
GCST90043942Jiang L2021110456,238A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR1
Tier 3: regulatory0
Tier 4: intronic/intergenic48

MAF distribution

BucketVariants
common (>=0.05)47
low_freq (0.01-0.05)0
rare (<0.01)1
unknown2

Functional consequences

ConsequenceCount
intron_variant27
intron_variant x intron_variant9
intergenic_variant5
non_coding_transcript_exon_variant2
intergenic_variant x intron_variant2
intergenic_variant x intergenic_variant2
intron_variant x intergenic_variant1
missense_variant1
5_prime_UTR_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs42730771716945825A>C,G,T0.05intron_variantTNFRSF13B2e-19Tier 4: intronic/intergenic
rs6781529341709841C>A,T0.164intron_variantULK41e-15Tier 4: intronic/intergenic
rs7577599225390277T>C0.05intron_variantDTNB8e-15Tier 4: intronic/intergenic
rs544095130595896279A>Tintron_variantELL24e-14Tier 4: intronic/intergenic
rs1716981341921170G>A,C,T0.05intron_variantULK41e-13Tier 4: intronic/intergenic
rs1151168566503573T>C0.008intron_variantEXOC22e-13Tier 4: intronic/intergenic
rs98112163169769713T>C,G0.05non_coding_transcript_exon_variantACTRT3 - MYNN2e-12Tier 4: intronic/intergenic
rs11085015193369574T>G0.05intron_variantNFIC7e-12Tier 4: intronic/intergenic
rs1953142238375835C>A,G,T0.05intron_variantTPTEP2, TPTEP2-CSNK1E4e-11Tier 4: intronic/intergenic
rs101180409 x 13115117135A>G,T0.05intron_variant x intron_variantDELEC1, TNC x CRYL17e-11Tier 4: intronic/intergenic
rs1295921318 x 2045189055G>A,C0.05intergenic_variant x intron_variantSETBP1 - SLC14A2 x PREX17e-11Tier 4: intronic/intergenic
rs15467172 x 15212037614A>C,G,T0.05intron_variant x intron_variantERBB4 x RORA9e-11Tier 4: intronic/intergenic
rs64557446 x 14161639436C>T0.05intron_variant x intergenic_variantPRKN x RN7SL714P - LINC029141e-10Tier 4: intronic/intergenic
rs246711212 x 2022918710C>A,T0.05intron_variant x intron_variantLINC02955 x TMC21e-10Tier 4: intronic/intergenic
rs6741351 x 1391210118G>A0.05intergenic_variant x intergenic_variantRPL5P6 - HFM1 x LINC01075 - LINC010741e-10Tier 4: intronic/intergenic
rs56219066595907227T>A,C0.289intron_variantELL22e-10Tier 4: intronic/intergenic
rs579684581716916785G>A,C0.098intron_variantCOTL1P1 - TBC1D27P3e-10Tier 4: intronic/intergenic
rs14379192 x 9211246115G>A0.05intergenic_variant x intron_variantCPS1 - RPS27P10 x PTPRD3e-10Tier 4: intronic/intergenic
rs10117807 x 1370659662A>C0.05intron_variant x intron_variantAUTS2 x HS6ST33e-10Tier 4: intronic/intergenic
rs26195663 x 32583254G>A,C,T0.05intron_variant x intron_variantCNTN4 x TAFA13e-10Tier 4: intronic/intergenic
rs2002038251336184459AC>A0.05intron_variantSOHLH2, CCDC169-SOHLH23e-10Tier 4: intronic/intergenic
rs17001128 x 94239896A>C,G0.05intron_variant x intron_variantCSMD1 x HMGB3P23 - RNA5SP2814e-10Tier 4: intronic/intergenic
rs49094948 x 12135634305C>A,G,T0.05intron_variant x intron_variantKHDRBS3 x KSR24e-10Tier 4: intronic/intergenic
rs8080346 x 10119146578A>G,T0.05intron_variant x intron_variantFAM184A x FRMD4A5e-10Tier 4: intronic/intergenic
rs78677719 x 1616314911C>G,T0.05intron_variant x intron_variantLINC03041 x CDH135e-10Tier 4: intronic/intergenic
rs501212713 x 17104466750A>G,T0.05intergenic_variant x intergenic_variantATP6V1G1P7 - RPL7P45 x ISCA1P3 - ARL2BPP85e-10Tier 4: intronic/intergenic
rs6919908631277183T>C,G0.23non_coding_transcript_exon_variantUSP8P16e-10Tier 4: intronic/intergenic
rs747404262173383237A>G0.05intergenic_variantCDCA7 - JPT1P16e-10Tier 4: intronic/intergenic
rs37474811630655046C>T0.05missense_variantPRR144e-09Tier 1: coding
rs2188127921965233C>G0.05intron_variantCDKN2A-AS16e-09Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
TNFRSF13BOrphanet:696907Common variable immunodeficiency phenotype due to homozygous TACI deficiency
ASXL2Orphanet:689408Shashi-Pena syndrome
DNAH11Orphanet:244Primary ciliary dyskinesia

Cohort genes → proteins

19 cohort genes, 19 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only19

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TOM1HGNC:11982ENSG00000100284O60784Target of Myb1 membrane trafficking proteingwas
MYNNHGNC:14955ENSG00000085274Q9NPC7Myoneuringwas
CBX7HGNC:1557ENSG00000100307O95931Chromobox protein homolog 7gwas
ULK4HGNC:15784ENSG00000168038Q96C45Serine/threonine-protein kinase ULK4gwas
ELL2HGNC:17064ENSG00000118985O00472RNA polymerase II elongation factor ELL2gwas
PSORS1C2HGNC:17199ENSG00000204538Q9UIG4Psoriasis susceptibility 1 candidate gene 2 proteingwas
RIMS2HGNC:17283ENSG00000176406Q9UQ26Regulating synaptic membrane exocytosis protein 2gwas
TNFRSF13BHGNC:18153ENSG00000240505O14836Tumor necrosis factor receptor superfamily member 13Bgwas
SFMBT2HGNC:20256ENSG00000198879Q5VUG0Scm-like with four MBT domains protein 2gwas
ASXL2HGNC:23805ENSG00000143970Q76L83Putative Polycomb group protein ASXL2gwas
CSNK1G1HGNC:2454ENSG00000169118Q9HCP0Casein kinase I isoform gamma-1gwas
TSNARE1HGNC:26437ENSG00000171045Q96NA8t-SNARE domain-containing protein 1gwas
SGMS2HGNC:28395ENSG00000164023Q8NHU3Phosphatidylcholine:ceramide cholinephosphotransferase 2gwas
LRRC34HGNC:28408ENSG00000171757Q8IZ02Leucine-rich repeat-containing protein 34gwas
DNAH11HGNC:2942ENSG00000105877Q96DT5Dynein axonemal heavy chain 11gwas
DTNBHGNC:3058ENSG00000138101O60941Dystrobrevin betagwas
CDCA7LHGNC:30777ENSG00000164649Q96GN5Cell division cycle-associated 7-like proteingwas
PROX1HGNC:9459ENSG00000117707Q92786Prospero homeobox protein 1gwas
RAD51BHGNC:9822ENSG00000182185O15315DNA repair protein RAD51 homolog 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TOM1Target of Myb1 membrane trafficking proteinAdapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways.
CBX7Chromobox protein homolog 7Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
ULK4Serine/threonine-protein kinase ULK4May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.
ELL2RNA polymerase II elongation factor ELL2Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.
RIMS2Regulating synaptic membrane exocytosis protein 2Rab effector involved in exocytosis.
TNFRSF13BTumor necrosis factor receptor superfamily member 13BReceptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity.
SFMBT2Scm-like with four MBT domains protein 2Transcriptional repressor of HOXB13 gene.
ASXL2Putative Polycomb group protein ASXL2Putative Polycomb group (PcG) protein.
CSNK1G1Casein kinase I isoform gamma-1Serine/threonine-protein kinase.
SGMS2Phosphatidylcholine:ceramide cholinephosphotransferase 2Sphingomyelin synthase that primarily contributes to sphingomyelin synthesis and homeostasis at the plasma membrane.
LRRC34Leucine-rich repeat-containing protein 34Highly expressed in stem cells where it may be involved in regulation of pluripotency.
DNAH11Dynein axonemal heavy chain 11Force generating protein required for cilia beating in respiratory epithelia.
DTNBDystrobrevin betaScaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids.
CDCA7LCell division cycle-associated 7-like proteinPlays a role in transcriptional regulation as a repressor that inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter.
PROX1Prospero homeobox protein 1Transcription factor involved in developmental processes such as cell fate determination, gene transcriptional regulation and progenitor cell regulation in a number of organs.
RAD51BDNA repair protein RAD51 homolog 2Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.

Protein-family classification

Druggable: 3 · Difficult: 5 · Unknown: 11 · Druggable fraction: 0.16

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
Transcription factor52.2×0.283
Kinase22.9×0.297
Other/Unknown111.0×0.697
Enzyme (other)10.6×0.809

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TOM1Other/UnknownnoVHS_dom, GAT_dom, ENTH_VHS
MYNNTranscription factornoBTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
CBX7Other/UnknownnoChromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromo_dom_subgr
ULK4KinaseyesProt_kinase_dom, Kinase-like_dom_sf, ARM-like
ELL2Other/UnknownnoOccludin_ELL, ELL_N, ELL/occludin
PSORS1C2Other/UnknownnoSPR1
RIMS2Transcription factornoC2_dom, PDZ, Rab_BD
TNFRSF13BOther/UnknownnoTACI_Cys-rich-dom, TNFR_13B
SFMBT2Other/UnknownnoSAM, Mbt, SAM/pointed_sf
ASXL2Other/UnknownnoAsxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
CSNK1G1Kinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TSNARE1Other/UnknownnoT_SNARE_dom, Syntaxin_N, SNARE
SGMS2Enzyme (other)yes2.7.8.27Sphingomyelin_synth-like_dom, Sphingomyelin_synth-like
LRRC34Other/UnknownnoLeu-rich_rpt, LRR_dom_sf, LRR-containing_regulator
DNAH11Other/UnknownnoAAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DTNBTranscription factornoZnf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1
CDCA7LTranscription factornoZnf-4CXXC_R1, CDCA7/CDA7L
PROX1Transcription factornoHomeodomain-like_sf, Homeo_prospero_dom, Homeo_prospero_dom_sf
RAD51BOther/UnknownnoAAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like

Expression context

Cohort genes with no expression data: 0.

17 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)19
unknown0

Top tissues across cohort

TissueCohort genes
secondary oocyte4
buccal mucosa cell3
sural nerve3
male germ line stem cell (sensu Vertebrata) in testis2
cartilage tissue2
skin of abdomen2
skin of leg2
bronchial epithelial cell2
bronchus2
gastrocnemius1
lower esophagus mucosa1
muscle of leg1
Brodmann (1909) area 101
cerebellar vermis1
paraflocculus1
decidua1
mucosa of paranasal sinus1
parotid gland1
zone of skin1
endothelial cell1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TOM1207ubiquitousmarkerlower esophagus mucosa, gastrocnemius, muscle of leg
MYNN274ubiquitousmarkerbuccal mucosa cell, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
CBX7296ubiquitousmarkercerebellar vermis, paraflocculus, Brodmann (1909) area 10
ULK4203ubiquitousmarkerdecidua, secondary oocyte, buccal mucosa cell
ELL2265ubiquitousmarkerparotid gland, mucosa of paranasal sinus, cartilage tissue
PSORS1C2114tissue_specificyesskin of leg, zone of skin, skin of abdomen
RIMS2198broadmarkerlateral nuclear group of thalamus, endothelial cell, middle temporal gyrus
TNFRSF13B158tissue_specificmarkertype B pancreatic cell, olfactory bulb, spleen
SFMBT2230ubiquitousmarkersural nerve, bone marrow cell, cartilage tissue
ASXL2288ubiquitousmarkercaput epididymis, corpus epididymis, cauda epididymis
CSNK1G1261ubiquitousmarkersecondary oocyte, esophagus squamous epithelium, left testis
TSNARE1185ubiquitousyespancreatic ductal cell, skin of abdomen, skin of leg
SGMS2233ubiquitousmarkertibia, secondary oocyte, epithelial cell of pancreas
LRRC34192broadmarkerbronchial epithelial cell, bronchus, sperm
DNAH11163broadmarkerright uterine tube, bronchial epithelial cell, bronchus
DTNB201ubiquitousmarkerC1 segment of cervical spinal cord, spinal cord, right frontal lobe
CDCA7L239ubiquitousmarkergerminal epithelium of ovary, primordial germ cell in gonad, ventricular zone
PROX1225broadmarkersural nerve, liver, right lobe of liver
RAD51B193ubiquitousmarkersural nerve, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ASXL24,417
RAD51B2,993
RIMS21,942
PROX11,688
DNAH111,666
MYNN1,548
TOM11,475
CDCA7L1,413
TNFRSF13B1,333
TSNARE11,288

Intra-cohort edges

ABSources
CDCA7LDNAH11string_interaction
CDCA7LULK4string_interaction
LRRC34MYNNstring_interaction

Structural data

PDB: 14 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CBX7O959318
TOM1O607846
RAD51BO153155
ELL2O004724
ULK4Q96C452
RIMS2Q9UQ262
TNFRSF13BO148362
CDCA7LQ96GN52
MYNNQ9NPC71
SFMBT2Q5VUG01
ASXL2Q76L831
CSNK1G1Q9HCP01
LRRC34Q8IZ021
PROX1Q927861

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SGMS2Q8NHU377.54
DTNBO6094176.29
PSORS1C2Q9UIG471.08
TSNARE1Q96NA868.69
DNAH11Q96DT5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 19 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Impaired BRCA2 binding to PALB2165.3×0.051RAD51B
Defective homologous recombination repair (HRR) due to BRCA1 loss of function160.4×0.051RAD51B
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function160.4×0.051RAD51B
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function160.4×0.051RAD51B
TNFs bind their physiological receptors156.3×0.051TNFRSF13B
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)156.3×0.051RAD51B
Homologous DNA Pairing and Strand Exchange154.4×0.051RAD51B
Formation of the dystrophin-glycoprotein complex (DGC)144.1×0.051DTNB
Resolution of D-loop Structures through Holliday Junction Intermediates142.9×0.051RAD51B
Sphingolipid de novo biosynthesis140.8×0.051SGMS2
Presynaptic phase of homologous DNA pairing and strand exchange138.8×0.051RAD51B
HDR through Homologous Recombination (HRR)127.2×0.066RAD51B
Sphingolipid metabolism124.0×0.069SGMS2
RNA polymerase II transcribes snRNA genes122.1×0.070ELL2
Deubiquitination117.7×0.076ASXL2
UCH proteinases117.7×0.076ASXL2
Factors involved in megakaryocyte development and platelet production19.5×0.130RAD51B
Metabolism of lipids14.5×0.247SGMS2
Neutrophil degranulation13.3×0.309TOM1
Post-translational protein modification12.7×0.344ASXL2
Metabolism of proteins11.8×0.467ASXL2
Metabolism11.7×0.468SGMS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
hepatocyte cell migration1936.2×0.020PROX1
protein kinase C deactivation1936.2×0.020ULK4
otic placode formation1936.2×0.020PROX1
branching involved in pancreas morphogenesis1936.2×0.020PROX1
positive regulation of cell cycle checkpoint1936.2×0.020PROX1
ceramide phosphoethanolamine biosynthetic process1936.2×0.020SGMS2
positive regulation of forebrain neuron differentiation1936.2×0.020PROX1
determination of left/right asymmetry in nervous system1468.1×0.029DNAH11
lens placode formation involved in camera-type eye formation1468.1×0.029PROX1
regulation of endosome organization1468.1×0.029TOM1
olfactory placode formation1312.1×0.030PROX1
ventricular cardiac myofibril assembly1312.1×0.030PROX1
lymphatic endothelial cell fate commitment1312.1×0.030PROX1
negative regulation of bile acid biosynthetic process1312.1×0.030PROX1
calcium ion-regulated exocytosis of neurotransmitter1234.1×0.030RIMS2
endocardium formation1234.1×0.030PROX1
aorta smooth muscle tissue morphogenesis1234.1×0.030PROX1
positive regulation of heart growth1234.1×0.030PROX1
substrate localization to autophagosome1234.1×0.030TOM1
blood vessel endothelial cell differentiation1187.2×0.030PROX1
acinar cell differentiation1187.2×0.030PROX1
protein localization to motile cilium1187.2×0.030DNAH11
blastocyst growth1156.0×0.030RAD51B
skeletal muscle thin filament assembly1156.0×0.030PROX1
positive regulation of sarcomere organization1156.0×0.030PROX1
spontaneous neurotransmitter secretion1156.0×0.030RIMS2
positive regulation of inhibitory postsynaptic potential1156.0×0.030RIMS2
venous blood vessel morphogenesis1133.8×0.030PROX1
atrial cardiac muscle tissue morphogenesis1133.8×0.030PROX1
embryonic retina morphogenesis in camera-type eye1133.8×0.030PROX1

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
Idecabtagene VicleucelApproved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Celecoxib, Daratumumab, Human Immunoglobulin G, Isatuximab, OMEGA-3 FATTY ACIDS, Zanubrutinib.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 17

Druggability breadth: 5 of 19 evidence-associated genes (26%) 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
CSNK1G1RUXOLITINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CSNK1G1224
CBX713
TOM100
MYNN00
ULK400
ELL200
PSORS1C200
RIMS200
TNFRSF13B00
SFMBT200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
RUXOLITINIB4CSNK1G1
BARICITINIB4CSNK1G1
SUNITINIB4CSNK1G1
SURAMIN3CBX7
LINIFANIB3CSNK1G1
ALVOCIDIB3CSNK1G1
SILMITASERTIB2CSNK1G1
SELICICLIB2CSNK1G1
CC-4012CSNK1G1
SU-0148132CSNK1G1
CENISERTIB2CSNK1G1
ILORASERTIB2CSNK1G1
TG100-1152CSNK1G1
TAK-7152CSNK1G1
ZEMIRCICLIB2CSNK1G1
BI-25362CSNK1G1
PF-005622711CSNK1G1
KW-24491CSNK1G1
GSK-10596151CSNK1G1
RGB-2866381CSNK1G1
LADUVIGLUSIB1CSNK1G1
CYC-1161CSNK1G1
AST-4871CSNK1G1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
CSNK1G1297Binding:296, Functional:1
CBX736Binding:35, Functional:1
SGMS230Binding:30
MYNN2Binding:2
PROX11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CSNK1G12.7.11.1non-specific serine/threonine protein kinase
SGMS22.7.8.27sphingomyelin synthase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CSNK1G1297

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

23 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)
RUXOLITINIB4CSNK1G1
BARICITINIB4CSNK1G1
SUNITINIB4CSNK1G1
SURAMIN3CBX7
LINIFANIB3CSNK1G1
ALVOCIDIB3CSNK1G1
SILMITASERTIB2CSNK1G1
SELICICLIB2CSNK1G1
CC-4012CSNK1G1
SU-0148132CSNK1G1
CENISERTIB2CSNK1G1
ILORASERTIB2CSNK1G1
TG100-1152CSNK1G1
TAK-7152CSNK1G1
ZEMIRCICLIB2CSNK1G1
BI-25362CSNK1G1
PF-005622711CSNK1G1
KW-24491CSNK1G1
GSK-10596151CSNK1G1
RGB-2866381CSNK1G1
LADUVIGLUSIB1CSNK1G1
CYC-1161CSNK1G1
AST-4871CSNK1G1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CSNK1G1
BPhased (≥1) drug, not yet approved1CBX7
CDruggable family + PDB, no drug1ULK4
DDruggable family + AlphaFold only, no drug1SGMS2
EDifficult family or no structure, no drug15TOM1, MYNN, ELL2, PSORS1C2, RIMS2, TNFRSF13B, SFMBT2, ASXL2, TSNARE1, LRRC34 (+5 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TOM10—
MYNN2—
ULK40—
ELL20—
PSORS1C20—
RIMS20—
TNFRSF13B0—
SFMBT20—
ASXL20—
TSNARE10—
SGMS230—
LRRC340—
DNAH110—
DTNB0—
CDCA7L0—
PROX11—
RAD51B0—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified9
PHASE22
PHASE41
EARLY_PHASE11
PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02920190PHASE4WITHDRAWNAntigen-Lipid-Driven Monoclonal Gammopathies Targeting Epicardial Fat
NCT03236428PHASE2ACTIVE_NOT_RECRUITINGPhase II Study of the CD38 Antibody Daratumumab in Patients With High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma
NCT04614558PHASE2RECRUITINGIsatuximab in Patients With Monoclonal Gammopathy of Renal Significance
NCT03820817PHASE1COMPLETEDRifaximin in Patients With Monoclonal Gammopathy
NCT03591614EARLY_PHASE1WITHDRAWNDendritic Cell DKK1 Vaccine for Monoclonal Gammopathy and Stable or Smoldering Myeloma
NCT05686447Not specifiedRECRUITINGScreening and Therapeutic Monitoring of Multiple Myeloma by MALDI-TOF MS Analysis
NCT06489613Not specifiedNOT_YET_RECRUITINGScreening for Monoclonal Gammopathy in Individuals Undergoing Physical Examinations Using iMS-LC Assay Technology.
NCT06750965Not specifiedNOT_YET_RECRUITINGMulti-center Screening for Serum M Protein
NCT06870760Not specifiedRECRUITINGPre-malignant States to Hematologic Malignancies in Firefighters
NCT07448779Not specifiedRECRUITINGInvestigating the Pathogenic Role of N-glycosylation in AL Amyloidosis: Molecular Bases, Diagnosis, and Treatment
NCT00173264Not specifiedUNKNOWNImmunologic and Genetic Characteristics of Monoclonal Immunoglobulins in Patient With Tuberculosis
NCT01543100Not specifiedCOMPLETEDPrognostic Study of Markers of Angiogenesis and Coagulability in Patients With Monoclonal Gammopathy
NCT02741999Not specifiedCOMPLETEDA Diagnostic Screening Trial Seeking AL Amyloidosis Very Early
NCT03832140Not specifiedCOMPLETEDFrequency and Characteristics of Pruritus in Patients With Monoclonal Gammopathy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
DARATUMUMAB41
ISATUXIMAB41
LIRAGLUTIDE41
CHEMBL43930501
CHEMBL452406601
CHEMBL464502901
CHEMBL478536601
CHEMBL521940501
CHEMBL527539701
CHEMBL528793401
CHEMBL540525701

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 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot