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Wilms tumor

disease
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Also known as Wilms tumor (nephroblastoma)Wilms tumour (nephroblastoma)Wilms' tumorWilms' tumour

Summary

Wilms tumor (MONDO:0006058) is a cancer with 11 cohort genes (8 CIViC-evidence somatic drivers; 14 ClinVar predisposition records) and 74 clinical trials. Top therapeutic interventions include cabozantinib, ensartinib, and erdafitinib.

At a glance

  • Classification: Cancer
  • Cohort genes: 11
  • ClinVar variants: 14
  • Clinical trials: 74

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameWilms tumor
Mondo IDMONDO:0006058
MeSHD009396
NCITC3267
UMLSC0027708
MedGen10221
GARD0027737
Is cancer (heuristic)yes

Also known as: Wilms tumor · Wilms tumor (nephroblastoma) · Wilms tumour (nephroblastoma) · Wilms’ tumor · Wilms’ tumour

Data availability: 14 ClinVar variants · 7 cell lines · 8 intOGen driver records.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › embryonal neoplasm › Wilms tumor

Related subtypes (11): notochordal tumor, rhabdoid tumor, primitive neuroectodermal tumor, blastoma, testicular embryonal carcinoma, medulloblastoma, pineoblastoma, congenital mesoblastic nephroma, intraocular medulloepithelioma, hepatoblastoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor

Subtypes (4): ovarian Wilms tumor, hereditary Wilms tumor, cervical Wilms tumor, kidney Wilms tumor

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

14 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 4 pathogenic, 3 other, 2 pathogenic; other, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
438773NM_007194.4(CHEK2):c.1100_1101del (p.Thr367fs)CHEK2Pathogenicno assertion criteria provided
17576NM_001904.4(CTNNB1):c.133_135del (p.Ser45del)CTNNB1Pathogenic; otherno assertion criteria provided
17588NM_001904.4(CTNNB1):c.134C>T (p.Ser45Phe)CTNNB1Pathogenic; otherno assertion criteria provided
438765NM_003506.4(FZD6):c.346C>T (p.Arg116Ter)FZD6Pathogeniccriteria provided, single submitter
973190NM_005762.3(TRIM28):c.2101C>T (p.Gln701Ter)TRIM28Pathogeniccriteria provided, single submitter
3062359NM_024426.6(WT1):c.1032C>G (p.Tyr344Ter)WT1Pathogeniccriteria provided, single submitter
438774NM_152383.5(DIS3L2):c.2381_2382del (p.Arg794fs)DIS3L2Likely pathogenicno assertion criteria provided
13961NM_004333.6(BRAF):c.1799T>A (p.Val600Glu)BRAFConflicting classifications of pathogenicitycriteria provided, conflicting classifications
2188763NM_000059.4(BRCA2):c.1556G>A (p.Ser519Asn)BRCA2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
406690NM_024426.6(WT1):c.411GCC[5] (p.Pro141dup)LOC107982234Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
184326NM_005359.6(SMAD4):c.875C>T (p.Pro292Leu)SMAD4Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
438758NM_001904.4(CTNNB1):c.770C>T (p.Thr257Ile)CTNNB1otherno assertion criteria provided
92220NM_005120.3(MED12):c.131G>A (p.Gly44Asp)MED12otherno assertion criteria provided
438791NM_001127208.3(TET2):c.4456T>C (p.Ser1486Pro)TET2otherno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 73 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
BRAFActBLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTCCIViC #5
BRCA2LoFBLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVACIViC #7
MED12ActALL,CESC,CLLSLL,GBM,LGGNOS,NBL,PRAD,PROSTATE,UCEC
WT1LoFAML,MEL,PAADCIViC #49
CHEK2ActBRCACIViC #8950
CTNNB1ActACC,COAD,COADREAD,ESCA,HCC,LIHB,LUAD,MBL,MEL,NSCLC,OVT,PAST,PRAD,PROSTATE,RMS,SKIN,SOFT_TISSUE,STAD,UCEC,WTCIViC #1290
TET2LoFAML,MDS,MLYM,NHL,PCM,RCC,SOFT_TISSUECIViC #55
SMAD4LoFBRCA,CESC,CHOL,COAD,COADREAD,ESCA,ESCC,GBC,HNSC,LUAD,NSCLC,PAAD,PANCREAS,PRAD,PROSTATE,READ,STAD,STOMACHCIViC #77

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BRAFOrphanet:1340Cardiofaciocutaneous syndrome
BRAFOrphanet:146Differentiated thyroid carcinoma
BRAFOrphanet:251615Pilomyxoid astrocytoma
BRAFOrphanet:389Langerhans cell histiocytosis
BRAFOrphanet:500Noonan syndrome with multiple lentigines
BRAFOrphanet:54595Craniopharyngioma
BRAFOrphanet:58017Classic hairy cell leukemia
BRAFOrphanet:626Large/giant congenital melanocytic nevus
BRAFOrphanet:648Noonan syndrome
BRAFOrphanet:840Syringocystadenoma papilliferum
BRAFOrphanet:96253Cushing disease
BRCA2Orphanet:1331Familial prostate cancer
BRCA2Orphanet:1333Familial pancreatic carcinoma
BRCA2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
BRCA2Orphanet:178Chordoma
BRCA2Orphanet:227535Hereditary breast cancer
BRCA2Orphanet:319462Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2Orphanet:440437Familial colorectal cancer Type X
BRCA2Orphanet:654Nephroblastoma
BRCA2Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
BRCA2Orphanet:694963Inflammatory breast cancer
BRCA2Orphanet:70567Cholangiocarcinoma
BRCA2Orphanet:84Fanconi anemia
MED12Orphanet:1415Hardikar syndrome
MED12Orphanet:293707Blepharophimosis-intellectual disability syndrome, MKB type
MED12Orphanet:776Lujan-Fryns syndrome
MED12Orphanet:777X-linked non-syndromic intellectual disability
MED12Orphanet:93932FG syndrome type 1
WT1Orphanet:220Denys-Drash syndrome
WT1Orphanet:24246,XY complete gonadal dysgenesis
WT1Orphanet:25151046,XY partial gonadal dysgenesis
WT1Orphanet:3097Meacham syndrome
WT1Orphanet:347Frasier syndrome
WT1Orphanet:654Nephroblastoma
WT1Orphanet:656Hereditary steroid-resistant nephrotic syndrome
WT1Orphanet:83469Desmoplastic small round cell tumor
WT1Orphanet:893WAGR syndrome
TRIM28Orphanet:654Nephroblastoma
CHEK2Orphanet:1331Familial prostate cancer
CHEK2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
CHEK2Orphanet:440437Familial colorectal cancer Type X
CHEK2Orphanet:524Li-Fraumeni syndrome
CHEK2Orphanet:668Osteosarcoma
CTNNB1Orphanet:1501Adrenocortical carcinoma
CTNNB1Orphanet:210159Adult hepatocellular carcinoma
CTNNB1Orphanet:2780Osteopathia striata-cranial sclerosis syndrome
CTNNB1Orphanet:33402Pediatric hepatocellular carcinoma
CTNNB1Orphanet:404473Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1Orphanet:54595Craniopharyngioma
CTNNB1Orphanet:569248Microcystic stromal tumor

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence11

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BRAFHGNC:1097ENSG00000157764P15056Serine/threonine-protein kinase B-rafclinvar
BRCA2HGNC:1101ENSG00000139618P51587Breast cancer type 2 susceptibility proteinclinvar
MED12HGNC:11957ENSG00000184634Q93074Mediator of RNA polymerase II transcription subunit 12clinvar
WT1HGNC:12796ENSG00000184937P19544Wilms tumor proteinclinvar
TRIM28HGNC:16384ENSG00000130726Q13263Transcription intermediary factor 1-betaclinvar
CHEK2HGNC:16627ENSG00000183765O96017Serine/threonine-protein kinase Chk2clinvar
CTNNB1HGNC:2514ENSG00000168036P35222Catenin beta-1clinvar
TET2HGNC:25941ENSG00000168769Q6N021Methylcytosine dioxygenase TET2clinvar
DIS3L2HGNC:28648ENSG00000144535Q8IYB7DIS3-like exonuclease 2clinvar
FZD6HGNC:4044ENSG00000164930O60353Frizzled-6clinvar
SMAD4HGNC:6770ENSG00000141646Q13485SMAD family member 4clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BRAFSerine/threonine-protein kinase B-rafProtein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
BRCA2Breast cancer type 2 susceptibility proteinInvolved in double-strand break repair and/or homologous recombination.
MED12Mediator of RNA polymerase II transcription subunit 12Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
WT1Wilms tumor proteinTranscription factor that plays an important role in cellular development and cell survival.
TRIM28Transcription intermediary factor 1-betaNuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs).
CHEK2Serine/threonine-protein kinase Chk2Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
CTNNB1Catenin beta-1Key downstream component of the canonical Wnt signaling pathway.
TET2Methylcytosine dioxygenase TET2Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
DIS3L2DIS3-like exonuclease 23’-5’-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3’ end and mediates their degradation.
FZD6Frizzled-6Receptor for Wnt proteins.
SMAD4SMAD family member 4In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.27

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
Kinase25.0×0.230
GPCR12.2×0.523
Transcription factor21.5×0.523
Other/Unknown61.0×0.654

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BRAFKinaseyes2.7.10.2Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
BRCA2Other/UnknownnoBRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
MED12Other/UnknownnoMediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
WT1Transcription factornoWilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
TRIM28Transcription factornoZnf_B-box, Bromodomain, Znf_RING
CHEK2Kinaseyes2.7.11.1FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
CTNNB1Other/UnknownnoArmadillo, ARM-like, Beta-catenin
TET2Other/Unknownno2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase
DIS3L2Other/UnknownnoRNase_II/R, NA-bd_OB-fold, RNase_II/R_CS
FZD6GPCRyesFrizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
SMAD4Other/UnknownnoSMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf

Expression context

Cohort genes with no expression data: 0.

11 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)11
unknown0

Top tissues across cohort

TissueCohort genes
ventricular zone4
buccal mucosa cell2
calcaneal tendon2
male germ line stem cell (sensu Vertebrata) in testis2
colonic epithelium1
secondary oocyte1
left ovary1
right adrenal gland1
right adrenal gland cortex1
germinal epithelium of ovary1
metanephric glomerulus1
renal glomerulus1
left testis1
right testis1
lower esophagus mucosa1
primordial germ cell in gonad1
adrenal tissue1
periodontal ligament1
amniotic fluid1
epithelium of nasopharynx1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BRAF265ubiquitousmarkerbuccal mucosa cell, colonic epithelium, calcaneal tendon
BRCA2184ubiquitousmarkermale germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
MED12281ubiquitousmarkerright adrenal gland cortex, right adrenal gland, left ovary
WT1168broadmarkergerminal epithelium of ovary, renal glomerulus, metanephric glomerulus
TRIM28145ubiquitousmarkerleft testis, right testis, ventricular zone
CHEK2183ubiquitousmarkerprimordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
CTNNB1295ubiquitousmarkeradrenal tissue, ventricular zone, periodontal ligament
TET2249ubiquitousmarkerpalpebral conjunctiva, amniotic fluid, epithelium of nasopharynx
DIS3L2241ubiquitousmarkersural nerve, sperm, buccal mucosa cell
FZD6260ubiquitousmarkerbronchial epithelial cell, caput epididymis, epithelium of bronchus
SMAD4288ubiquitousmarkerventricular zone, ganglionic eminence, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CTNNB115,668
TRIM288,167
BRAF7,394
SMAD47,320
BRCA24,839
CHEK24,795
WT13,938
MED123,322
DIS3L23,167
TET22,965

Intra-cohort edges

ABSources
BRAFBRCA2biogrid_interaction
BRCA2CHEK2string_interaction
CTNNB1MED12string_interaction
CTNNB1SMAD4string_interaction
TET2WT1intact

Structural data

PDB: 11 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
BRAFP15056131
CTNNB1P3522250
CHEK2O9601738
WT1P1954428
BRCA2P5158714
SMAD4Q1348512
TRIM28Q1326310
TET2Q6N0216
DIS3L2Q8IYB74
MED12Q930743
FZD6O603532

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 191. Enrichment computed across 11 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Formation of definitive endoderm2129.8×0.011CTNNB1, SMAD4
Germ layer formation at gastrulation2122.1×0.011CTNNB1, SMAD4
Cardiogenesis276.9×0.019CTNNB1, SMAD4
Epigenetic regulation of gene expression319.5×0.020MED12, TRIM28, TET2
Disease56.0×0.031BRAF, BRCA2, MED12, TRIM28, SMAD4
Loss of Function of SMAD4 in Cancer1346.1×0.039SMAD4
SMAD4 MH2 Domain Mutants in Cancer1346.1×0.039SMAD4
SMAD2/3 MH2 Domain Mutants in Cancer1346.1×0.039SMAD4
Impaired BRCA2 translocation to the nucleus1346.1×0.039BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)1346.1×0.039BRCA2
Reproduction234.6×0.039BRCA2, TET2
Ca2+ pathway232.4×0.039CTNNB1, FZD6
Adipogenesis228.4×0.039MED12, SMAD4
Gene expression (Transcription)46.5×0.039MED12, TRIM28, TET2, SMAD4
TET1,2,3 and TDG demethylate DNA1259.6×0.046TET2
Signaling by MRAS-complex mutants1259.6×0.046BRAF
Signalling to p38 via RIT and RIN1207.6×0.046BRAF
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production1207.6×0.046CTNNB1
RUNX3 regulates BCL2L11 (BIM) transcription1207.6×0.046SMAD4
Loss of Function of SMAD2/3 in Cancer1173.0×0.046SMAD4
Signaling by TGF-beta Receptor Complex in Cancer1173.0×0.046SMAD4
Negative feedback regulation of MAPK pathway1173.0×0.046BRAF
ARMS-mediated activation1148.3×0.046BRAF
RUNX3 regulates CDKN1A transcription1148.3×0.046SMAD4
CDH11 homotypic and heterotypic interactions1148.3×0.046CTNNB1
Prolonged ERK activation events1129.8×0.046BRAF
SHOC2 M1731 mutant abolishes MRAS complex function1129.8×0.046BRAF
Gain-of-function MRAS complexes activate RAF signaling1129.8×0.046BRAF
Regulation of CDH19 Expression and Function1129.8×0.046CTNNB1
Signaling by RNF43 mutants1115.3×0.046FZD6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of DNA-templated transcription717.8×8e-06BRCA2, MED12, WT1, TRIM28, CHEK2, CTNNB1, SMAD4
branching involved in ureteric bud morphogenesis399.9×6e-04WT1, CTNNB1, SMAD4
epithelial to mesenchymal transition385.1×6e-04TRIM28, CTNNB1, SMAD4
mesenchymal to epithelial transition2278.6×0.002WT1, CTNNB1
gastrulation with mouth forming second2170.2×0.004CTNNB1, SMAD4
male genitalia development2161.3×0.004WT1, CTNNB1
embryonic brain development2145.9×0.004MED12, CTNNB1
negative regulation of canonical Wnt signaling pathway332.1×0.004CTNNB1, FZD6, SMAD4
negative regulation of cell population proliferation415.3×0.004WT1, CTNNB1, DIS3L2, SMAD4
adrenal gland development2122.6×0.004WT1, SMAD4
positive regulation of gene expression414.1×0.004BRAF, WT1, CTNNB1, SMAD4
negative regulation of transcription by RNA polymerase II58.1×0.006WT1, TRIM28, CTNNB1, FZD6, SMAD4
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator290.1×0.006BRCA2, CHEK2
Wnt signaling pathway, planar cell polarity pathway282.8×0.007MED12, FZD6
regulation of DNA-templated transcription411.5×0.007BRCA2, WT1, CHEK2, SMAD4
negative regulation of DNA-templated transcription411.5×0.007WT1, TRIM28, CTNNB1, SMAD4
stem cell population maintenance276.6×0.007CTNNB1, DIS3L2
T cell differentiation in thymus274.7×0.007BRAF, CTNNB1
obsolete positive regulation of cell proliferation involved in heart valve morphogenesis11532.0×0.008SMAD4
glial cell fate determination11532.0×0.008CTNNB1
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation11532.0×0.008CTNNB1
female gonad morphogenesis11532.0×0.008SMAD4
cranial ganglion development11532.0×0.008CTNNB1
negative regulation of metanephric glomerular mesangial cell proliferation11532.0×0.008WT1
negative regulation of cardiac myofibril assembly11532.0×0.008SMAD4
DNA damage response, signal transduction by p53 class mediator265.2×0.008BRCA2, CHEK2
thymus development261.3×0.008BRAF, CTNNB1
positive regulation of epithelial to mesenchymal transition257.8×0.008CTNNB1, SMAD4
ERK1 and ERK2 cascade257.8×0.008BRAF, SMAD4
embryonic digit morphogenesis254.7×0.008CTNNB1, SMAD4

Therapeutics

Drugs indicated for this disease

1 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
DactinomycinApproved (phase 4)
EtoposidePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Carboplatin, Doxorubicin, Filgrastim, Ifosfamide, Irinotecan, Pegfilgrastim, Topotecan, Vincristine.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 6

Druggability breadth: 9 of 11 evidence-associated genes (82%) 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
BRAFVEMURAFENIB
CHEK2NERATINIB
CTNNB1DITHIAZANINE IODIDE
TET2VADADUSTAT

Top cohort targets by molecule count

SymbolMoleculesMax phase
BRAF484
CHEK2304
CTNNB144
TET234
MED1212
BRCA200
WT100
TRIM2800
DIS3L200
FZD600

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VEMURAFENIB4BRAF
PONATINIB4BRAF
FEDRATINIB4BRAF
SORAFENIB4BRAF
DASATINIB ANHYDROUS4BRAF
RUXOLITINIB4BRAF
INFIGRATINIB PHOSPHATE4BRAF
INFIGRATINIB4BRAF
REGORAFENIB4BRAF
DABRAFENIB4BRAF
COBIMETINIB4BRAF
NILOTINIB4BRAF
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF
DASATINIB4BRAF
ERLOTINIB4BRAF
GEFITINIB4BRAF, CHEK2
IMATINIB4BRAF
NERATINIB4CHEK2
BOSUTINIB4CHEK2
BRIGATINIB4CHEK2
SUNITINIB4CHEK2
DITHIAZANINE IODIDE4CTNNB1
VADADUSTAT4TET2
PANOBINOSTAT4TET2
DEFEROXAMINE4TET2
MASITINIB3BRAF
AVUTOMETINIB3BRAF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
BRAF1,442Binding:1400, Functional:37, ADMET:5
CHEK2690Binding:687, Functional:2, ADMET:1
CTNNB1361Binding:358, Functional:3
TET224Binding:24
TRIM2819Binding:19
MED126Binding:6
SMAD46Binding:6
DIS3L22Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BRAF2.7.10.2, 2.7.11.1non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
CHEK22.7.11.1non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BRAF1,442
CHEK2690
CTNNB1361

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

CompoundMax phaseCohort target (bioactivity)
PONATINIB4BRAF
FEDRATINIB4BRAF
SORAFENIB4BRAF
DASATINIB ANHYDROUS4BRAF
RUXOLITINIB4BRAF
INFIGRATINIB PHOSPHATE4BRAF
INFIGRATINIB4BRAF
REGORAFENIB4BRAF
DABRAFENIB4BRAF
COBIMETINIB4BRAF
NILOTINIB4BRAF
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF
DASATINIB4BRAF
ERLOTINIB4BRAF
GEFITINIB4BRAF, CHEK2
IMATINIB4BRAF
NERATINIB4CHEK2
BOSUTINIB4CHEK2
BRIGATINIB4CHEK2
SUNITINIB4CHEK2
DITHIAZANINE IODIDE4CTNNB1
VADADUSTAT4TET2
PANOBINOSTAT4TET2
DEFEROXAMINE4TET2
MASITINIB3BRAF
AVUTOMETINIB3BRAF

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4BRAF, CHEK2, CTNNB1, TET2
BPhased (≥1) drug, not yet approved1MED12
CDruggable family + PDB, no drug1FZD6
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug5BRCA2, WT1, TRIM28, DIS3L2, SMAD4

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SMAD46CTNNB1
BRCA20—
WT10—
TRIM2819—
DIS3L22—
FZD60—

Clinical trials & evidence

Clinical trials

Clinical trials: 74.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE125
PHASE222
Not specified21
PHASE1/PHASE24
PHASE41
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00336531PHASE4COMPLETEDEfficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT02867592PHASE2ACTIVE_NOT_RECRUITINGCabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714PHASE2ACTIVE_NOT_RECRUITINGErdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652PHASE2ACTIVE_NOT_RECRUITINGEnsartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03698994PHASE2ACTIVE_NOT_RECRUITINGUlixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555PHASE2ACTIVE_NOT_RECRUITINGIvosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04320888PHASE2ACTIVE_NOT_RECRUITINGSelpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04851119PHASE1/PHASE2RECRUITINGTegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
NCT04901702PHASE1/PHASE2RECRUITINGStudy of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma
NCT04968990PHASE2RECRUITINGTreatment of Newly Diagnosed Patient’s With Wilm’s Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation
NCT05384821PHASE1/PHASE2RECRUITINGMetronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)
NCT05985161PHASE2RECRUITINGA Study of Selinexor in People With Wilms Tumors and Other Solid Tumors
NCT00038207PHASE2COMPLETEDLiposomal Vincristine for Pediatric and Adolescent Patients With Relapsed Malignancies
NCT00141765PHASE2COMPLETEDStudy of High-Dose Chemotherapy With Bone Marrow or Stem Cell Transplant for Rare Poor-Prognosis Cancers
NCT00187031PHASE2COMPLETEDA Phase II Study of Topotecan in Children With Recurrent Wilms Tumor
NCT01095926PHASE2COMPLETEDPharmacokinetic Study of Doxorubicin in Children With Cancer
NCT02452554PHASE2COMPLETEDLorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT02581384PHASE1/PHASE2TERMINATEDStereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors
NCT02624388PHASE2TERMINATEDStudy of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02689336PHASE2WITHDRAWNErlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03213665PHASE2COMPLETEDTazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678PHASE2COMPLETEDSamotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03220035PHASE2COMPLETEDVemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204PHASE2COMPLETEDOlaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT04791228PHASE2WITHDRAWNA Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
NCT05302921PHASE2COMPLETEDNeoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT03618381PHASE1ACTIVE_NOT_RECRUITINGEGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04308330PHASE1RECRUITINGVorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
NCT04377932PHASE1ACTIVE_NOT_RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
NCT04483778PHASE1ACTIVE_NOT_RECRUITINGB7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04715191PHASE1RECRUITINGInterleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
NCT04897321PHASE1RECRUITINGB7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
NCT05103631PHASE1ACTIVE_NOT_RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors
NCT06198296PHASE1RECRUITINGImmunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells
NCT07148050PHASE1RECRUITINGImmunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells
NCT07172958PHASE1RECRUITINGSelective Antigen Specific T Cells and CAR T Cells in Subjects With Relapsed/Refractory Embryonal Tumors (SABRE)
NCT07584499PHASE1RECRUITINGPhase I Study of Becotatug Vedotin for Safety and Efficacy in EGFR-Positive Pediatric Relapsed/Refractory or Metastatic Solid Tumors
NCT00011414PHASE1COMPLETEDPhase I Trial of Tariquidar (XR9576) in Combination With Doxorubicin, Vinorelbine, or Docetaxel in Pediatric Patients With Solid Tumors
NCT00436657PHASE1COMPLETEDContinuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin for Children With Peritoneal Cancer

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
CABOZANTINIB43
ENSARTINIB42
ERDAFITINIB42
IVOSIDENIB42
LAROTRECTINIB42
SELPERCATINIB42
SELUMETINIB42
TAZEMETOSTAT42
VEMURAFENIB42
ITRACONAZOLE41
PEGFILGRASTIM41
SELINEXOR41
TOPOTECAN41
BECOTATUG VEDOTIN31
DOCIPARSTAT SODIUM31
GALINPEPIMUT-S31
TARIQUIDAR31
TIPIFARNIB31
SAMOTOLISIB22
ULIXERTINIB22
ENOBLITUZUMAB21
GENISTEIN21
LORVOTUZUMAB MERTANSINE21
TEGAVIVINT21
CHEMBL341555302
CHEMBL420955502
CHEMBL539843102
CHEMBL543081002
PLX-472002
CHEMBL421550101

About this page

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

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Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot