childhood kidney Wilms tumor

Summary

childhood kidney Wilms tumor (MONDO:0024676) is a cancer caused by TRIM28 (GenCC Definitive), with 3 cohort genes (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 79 clinical trials. Top therapeutic interventions include larotrectinib, cabozantinib, and dactinomycin.

At a glance

• Classification: Cancer
• Causal gene: TRIM28 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1
• Clinical trials: 79

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood kidney Wilms tumor
Mondo ID	MONDO:0024676
NCIT	C27730
UMLS	C1333015
MedGen	232073
GARD	0025457
Is cancer (heuristic)	yes

Also known as: childhood kidney Wilms tumor · childhood renal Wilms tumor · childhood renal Wilms tumour · childhood renal Wilms’ tumor · childhood renal Wilms’ tumour · childhood Wilms tumor · childhood Wilms tumour · kidney Wilms tumor · kidney Wilms tumour · Wilms tumor · Wilms tumour

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records · 59 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › malignant urinary system neoplasm › kidney cancer › kidney Wilms tumor › childhood kidney Wilms tumor

Related subtypes (7): nonanaplastic kidney Wilms tumor, metachronous kidney Wilms’ tumor, mixed cell type kidney Wilms’ tumor, blastema predominant kidney Wilms tumor, epithelial predominant Wilms’ tumor, stromal predominant kidney Wilms tumor, adult kidney Wilms tumor

Subtypes (1): cystic partially differentiated nephroblastoma

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3767320	NM_005612.5(REST):c.1135C>T (p.His379Tyr)	REST	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
REST	LoF	WT

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
TRIM28	Definitive	Autosomal dominant	childhood kidney Wilms tumor	2
CTR9	Moderate	Autosomal dominant	childhood kidney Wilms tumor	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRIM28	Orphanet:654	Nephroblastoma
CTR9	Orphanet:528084	Non-specific syndromic intellectual disability
CTR9	Orphanet:654	Nephroblastoma
REST	Orphanet:2024	Hereditary gingival fibromatosis
REST	Orphanet:654	Nephroblastoma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRIM28	HGNC:16384	ENSG00000130726	Q13263	Transcription intermediary factor 1-beta	gencc
CTR9	HGNC:16850	ENSG00000198730	Q6PD62	RNA polymerase-associated protein CTR9 homolog	gencc
REST	HGNC:9966	ENSG00000084093	Q13127	RE1-silencing transcription factor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIM28	Transcription intermediary factor 1-beta	Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs).
CTR9	RNA polymerase-associated protein CTR9 homolog	Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency.
REST	RE1-silencing transcription factor	Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.0

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
Transcription factor	2	5.5×	0.081
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRIM28	Transcription factor	no		Znf_B-box, Bromodomain, Znf_RING
CTR9	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Ctr9
REST	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_domain

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
ventricular zone	1
corpus epididymis	1
epithelium of nasopharynx	1
palpebral conjunctiva	1
male germ line stem cell (sensu Vertebrata) in testis	1
mucosa of paranasal sinus	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIM28	145	ubiquitous	marker	left testis, right testis, ventricular zone
CTR9	292	ubiquitous	marker	corpus epididymis, epithelium of nasopharynx, palpebral conjunctiva
REST	281	ubiquitous	marker	primordial germ cell in gonad, mucosa of paranasal sinus, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIM28	8,167
CTR9	4,367
REST	2,499

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTR9	Q6PD62	21
TRIM28	Q13263	10
REST	Q13127	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of NPAS4 gene transcription	1	761.3×	0.035	REST
Regulation of endogenous retroelements	1	122.8×	0.041	TRIM28
Dengue virus activates/modulates innate and adaptive immune responses	1	112.0×	0.041	CTR9
HCMV Infection	1	108.8×	0.041	TRIM28
NGF-stimulated transcription	1	95.2×	0.041	REST
SUMOylation of transcription cofactors	1	81.0×	0.041	TRIM28
Formation of RNA Pol II elongation complex	1	64.5×	0.041	CTR9
RNA Polymerase II Transcription Elongation	1	64.5×	0.041	CTR9
E3 ubiquitin ligases ubiquitinate target proteins	1	64.5×	0.041	CTR9
SUMO E3 ligases SUMOylate target proteins	1	59.5×	0.041	TRIM28
Regulation of PTEN gene transcription	1	59.5×	0.041	REST
SUMOylation	1	54.4×	0.041	TRIM28
RNA Polymerase II Pre-transcription Events	1	45.9×	0.044	CTR9
HDACs deacetylate histones	1	40.1×	0.044	REST
Potential therapeutics for SARS	1	38.1×	0.044	REST
CHD1 and CHD2 subfamily	1	36.2×	0.044	CTR9
Regulation of endogenous retroelements by KRAB-ZFP proteins	1	35.6×	0.044	TRIM28
HCMV Early Events	1	27.0×	0.055	TRIM28
Epigenetic regulation of gene expression	1	23.8×	0.059	TRIM28
Viral Infection Pathways	1	10.3×	0.127	TRIM28
Infectious disease	1	8.3×	0.149	TRIM28
RNA Polymerase II Transcription	1	7.5×	0.156	TRIM28
Post-translational protein modification	1	6.4×	0.174	TRIM28
Gene expression (Transcription)	1	6.0×	0.179	TRIM28
Generic Transcription Pathway	1	5.0×	0.201	TRIM28
Disease	1	4.4×	0.220	TRIM28
Metabolism of proteins	1	4.1×	0.223	TRIM28

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of dense core granule biogenesis	1	5617.3×	0.004	REST
negative regulation of amniotic stem cell differentiation	1	5617.3×	0.004	REST
negative regulation of transcription by RNA polymerase II	3	17.7×	0.004	TRIM28, CTR9, REST
modification of synaptic structure	1	2808.7×	0.005	REST
negative regulation of mesenchymal stem cell differentiation	1	2808.7×	0.005	REST
negative regulation of aldosterone biosynthetic process	1	1404.3×	0.006	REST
negative regulation of cortisol biosynthetic process	1	1404.3×	0.006	REST
convergent extension involved in axis elongation	1	1123.5×	0.006	TRIM28
embryonic placenta morphogenesis	1	1123.5×	0.006	TRIM28
endodermal cell fate commitment	1	936.2×	0.006	CTR9
inner cell mass cell differentiation	1	936.2×	0.006	CTR9
blastocyst growth	1	936.2×	0.006	CTR9
negative regulation of calcium ion-dependent exocytosis	1	624.1×	0.008	REST
negative regulation of single stranded viral RNA replication via double stranded DNA intermediate	1	510.7×	0.008	TRIM28
cardiac muscle cell myoblast differentiation	1	468.1×	0.008	REST
host-mediated suppression of viral transcription	1	432.1×	0.008	REST
regulation of osteoblast differentiation	1	432.1×	0.008	REST
cellular response to electrical stimulus	1	432.1×	0.008	REST
nervous system process	1	401.2×	0.008	REST
positive regulation of programmed cell death	1	374.5×	0.008	REST
interleukin-6-mediated signaling pathway	1	374.5×	0.008	CTR9
trophectodermal cell differentiation	1	330.4×	0.008	CTR9
suppression of viral release by host	1	330.4×	0.008	TRIM28
genomic imprinting	1	330.4×	0.008	TRIM28
negative regulation of myeloid cell differentiation	1	312.1×	0.008	CTR9
detection of mechanical stimulus involved in sensory perception of sound	1	312.1×	0.008	REST
negative regulation of DNA-templated transcription	2	21.0×	0.008	TRIM28, REST
cellular response to stress	1	280.9×	0.008	REST
auditory receptor cell stereocilium organization	1	280.9×	0.008	REST
positive regulation of DNA-templated transcription	2	18.6×	0.008	TRIM28, REST

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTR9	1	2
TRIM28	0	0
REST	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CTR9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TRIM28	19	Binding:19
CTR9	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	CTR9

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	1	CTR9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	TRIM28, REST

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TRIM28	19	—
REST	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 79.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	25
PHASE1	23
Not specified	22
PHASE1/PHASE2	4
PHASE3	3
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00336531	PHASE4	COMPLETED	Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT00352534	PHASE3	ACTIVE_NOT_RECRUITING	Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms’ Tumor
NCT00379340	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms’ Tumor
NCT00945009	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted 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)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib 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)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04322318	PHASE2	RECRUITING	A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
NCT04851119	PHASE1/PHASE2	RECRUITING	Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
NCT04901702	PHASE1/PHASE2	RECRUITING	Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma
NCT04968990	PHASE2	RECRUITING	Treatment of Newly Diagnosed Patient’s With Wilm’s Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation
NCT05384821	PHASE1/PHASE2	RECRUITING	Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)
NCT05985161	PHASE2	RECRUITING	A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors
NCT00141765	PHASE2	COMPLETED	Study of High-Dose Chemotherapy With Bone Marrow or Stem Cell Transplant for Rare Poor-Prognosis Cancers
NCT00187031	PHASE2	COMPLETED	A Phase II Study of Topotecan in Children With Recurrent Wilms Tumor
NCT01095926	PHASE2	COMPLETED	Pharmacokinetic Study of Doxorubicin in Children With Cancer
NCT02452554	PHASE2	COMPLETED	Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT02581384	PHASE1/PHASE2	TERMINATED	Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors
NCT02624388	PHASE2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03213665	PHASE2	COMPLETED	Tazemetostat 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)
NCT03213678	PHASE2	COMPLETED	Samotolisib 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)
NCT03220035	PHASE2	COMPLETED	Vemurafenib 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)
NCT03233204	PHASE2	COMPLETED	Olaparib 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)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT04791228	PHASE2	WITHDRAWN	A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
NCT05302921	PHASE2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT03618381	PHASE1	ACTIVE_NOT_RECRUITING	EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04308330	PHASE1	RECRUITING	Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
NCT04377932	PHASE1	ACTIVE_NOT_RECRUITING	Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
NCT04483778	PHASE1	ACTIVE_NOT_RECRUITING	B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04715191	PHASE1	RECRUITING	Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
NCT04897321	PHASE1	RECRUITING	B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
NCT05103631	PHASE1	ACTIVE_NOT_RECRUITING	Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LAROTRECTINIB	4	4
CABOZANTINIB	4	3
DACTINOMYCIN	4	3
ENSARTINIB	4	2
ERDAFITINIB	4	2
IVOSIDENIB	4	2
SELPERCATINIB	4	2
SELUMETINIB	4	2
TAZEMETOSTAT	4	2
VEMURAFENIB	4	2
ITRACONAZOLE	4	1
PEGFILGRASTIM	4	1
SELINEXOR	4	1
TALAZOPARIB	4	1
TOPOTECAN	4	1
TIPIFARNIB	3	2
BECOTATUG VEDOTIN	3	1
GALINPEPIMUT-S	3	1
SAMOTOLISIB	2	2
ULIXERTINIB	2	2
ENOBLITUZUMAB	2	1
GENISTEIN	2	1
LORVOTUZUMAB MERTANSINE	2	1
TEGAVIVINT	2	1
CHEMBL4748391	0	3
CHEMBL3415553	0	2
CHEMBL4209555	0	2
CHEMBL5398431	0	2
CHEMBL5430810	0	2
PLX-4720	0	2