Childhood kidney cell carcinoma

Summary

Childhood kidney cell carcinoma (MONDO:0003007) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 289 clinical trials. Top therapeutic interventions include cabozantinib, sunitinib, and sorafenib.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 289

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood kidney cell carcinoma
Mondo ID	MONDO:0003007
DOID	DOID:4454
NCIT	C6568
UMLS	C1333001
MedGen	232070
GARD	0023325
Is cancer (heuristic)	yes

Also known as: childhood kidney cell carcinoma · childhood renal cell carcinoma · childhood renal cell carcinoma (disease) · paediatric kidney cell carcinoma · paediatric renal cell carcinoma · paediatric renal cell carcinoma (disease) · pediatric kidney cell carcinoma · pediatric renal cell carcinoma · pediatric renal cell carcinoma (disease) · renal cell cancer · renal cell carcinoma (disease) of childhood

Data availability: 1 ClinVar variant.

Disease family

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › renal cell carcinoma › renal cell adenocarcinoma › childhood kidney cell carcinoma

Related subtypes (8): hereditary renal cell carcinoma, sarcomatoid renal cell carcinoma, clear cell renal carcinoma, renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions, papillary renal cell carcinoma, chromophobe renal cell carcinoma, renal cell carcinoma associated with neuroblastoma, tubulocystic renal cell carcinoma

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
412075	NM_177438.3(DICER1):c.3713T>C (p.Leu1238Pro)	DICER1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
DICER1	LoF	COADREAD,CSCC,MEL,UCEC	CIViC #9533

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DICER1	Orphanet:276399	Familial multinodular goiter
DICER1	Orphanet:284343	DICER1 tumor-predisposition syndrome
DICER1	Orphanet:404476	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome
DICER1	Orphanet:99757	Embryonal rhabdomyosarcoma
DICER1	Orphanet:99914	Gynandroblastoma
DICER1	Orphanet:99915	Malignant granulosa cell tumor of the ovary
DICER1	Orphanet:99916	Malignant Sertoli-Leydig cell tumor of the ovary

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DICER1	Endoribonuclease Dicer	Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DICER1	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, Helicase_C-like, PAZ_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
caput epididymis	1
cauda epididymis	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DICER1	295	ubiquitous	marker	cauda epididymis, caput epididymis, tongue squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DICER1	8,268

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DICER1	Q9UPY3	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis	1	3806.7×	0.001	DICER1
Small interfering RNA (siRNA) biogenesis	1	1142.0×	0.002	DICER1
Regulation of MITF-M-dependent genes involved in apoptosis	1	634.4×	0.003	DICER1
MicroRNA (miRNA) biogenesis	1	456.8×	0.003	DICER1
M-decay: degradation of maternal mRNAs by maternally stored factors	1	326.3×	0.003	DICER1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of Schwann cell differentiation	1	8426.0×	0.001	DICER1
peripheral nervous system myelin formation	1	5617.3×	0.001	DICER1
global gene silencing by mRNA cleavage	1	5617.3×	0.001	DICER1
tRNA decay	1	3370.4×	0.001	DICER1
negative regulation of Schwann cell proliferation	1	2407.4×	0.001	DICER1
siRNA processing	1	1872.4×	0.002	DICER1
RISC complex assembly	1	1532.0×	0.002	DICER1
miRNA metabolic process	1	1404.3×	0.002	DICER1
apoptotic DNA fragmentation	1	1203.7×	0.002	DICER1
pre-miRNA processing	1	1123.5×	0.002	DICER1
miRNA processing	1	1053.2×	0.002	DICER1
nerve development	1	936.2×	0.002	DICER1
positive regulation of myelination	1	766.0×	0.002	DICER1
negative regulation of tumor necrosis factor-mediated signaling pathway	1	455.5×	0.003	DICER1
neuron projection morphogenesis	1	276.3×	0.004	DICER1
negative regulation of tumor necrosis factor production	1	251.5×	0.004	DICER1
negative regulation of gene expression	1	69.1×	0.015	DICER1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	DICER1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DICER1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DICER1	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DICER1	3.1.26.3	ribonuclease III

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DICER1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DICER1	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 289.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	96
Not specified	63
PHASE1	60
PHASE1/PHASE2	42
PHASE3	16
PHASE4	6
EARLY_PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06903312	PHASE4	RECRUITING	Primary Tumor Ablation and Outcome in Metastatic Renal Cell Carcinoma Treated With Immunotherapy Combinations.
NCT06934057	PHASE4	RECRUITING	Cabozantinib and Nivolumab Among Older Patients With Renal Cell Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00172003	PHASE4	COMPLETED	Effect of Zoledronic Acid in Patients With Renal Cell Cancer and Bone Metastasis
NCT01402089	PHASE4	COMPLETED	Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
NCT02555748	PHASE4	COMPLETED	Therapeutic Drug Monitoring of Sunitinib and Pazopanib in Advanced or Metastatic Renal Cell Carcinoma
NCT01575548	PHASE3	ACTIVE_NOT_RECRUITING	Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer Who Have No Evidence of Disease After Surgery
NCT03055013	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
NCT03793166	PHASE3	ACTIVE_NOT_RECRUITING	Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
NCT04510597	PHASE3	RECRUITING	Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial
NCT05863351	PHASE3	ACTIVE_NOT_RECRUITING	Focused Radiation Versus Systemic Therapy for Kidney Cancer Patients With Limited Metastasis, SOAR Study
NCT06500455	PHASE3	RECRUITING	Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain
NCT07197580	PHASE3	RECRUITING	Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC
NCT07383441	PHASE3	NOT_YET_RECRUITING	Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer
NCT00061178	PHASE3	WITHDRAWN	Efficacy and Safety Study of rhuMAb VEGF to Treat Metastatic Renal Cell Carcinoma
NCT00311467	PHASE3	TERMINATED	Combined Treatment With Capecitabine and Immunotherapy Versus Immunotherapy Alone in Advanced Renal Cell Carcinoma
NCT00326898	PHASE3	COMPLETED	Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery
NCT00738530	PHASE3	COMPLETED	A Study of Avastin (Bevacizumab) Added to Interferon Alfa-2a (Roferon) Therapy in Patients With Metastatic Renal Cell Cancer With Nephrectomy
NCT01198158	PHASE3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT02684006	PHASE3	COMPLETED	A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)
NCT03095040	PHASE3	UNKNOWN	CM082 Combined With Everolimus in Chinese Patients With Metastatic Renal Cell Carcinoma
NCT04588246	PHASE3	TERMINATED	Comparing Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in Patients With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
NCT01038778	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer
NCT01684397	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
NCT02721732	PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic
NCT02830724	PHASE1/PHASE2	RECRUITING	Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
NCT03092856	PHASE2	ACTIVE_NOT_RECRUITING	Axitinib With or Without Anti-OX40 Antibody PF-04518600 in Treating Patients With Metastatic Kidney Cancer
NCT03284385	PHASE2	ACTIVE_NOT_RECRUITING	Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2
NCT03541902	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib or Sunitinib Malate in Treating Participants With Metastatic Variant Histology Renal Cell Carcinoma
NCT03587662	PHASE2	ACTIVE_NOT_RECRUITING	Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
NCT03595124	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Compare Treatments for a Type of Kidney Cancer Called TFE/Translocation Renal Cell Carcinoma (tRCC)
NCT03634540	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)
NCT03682289	PHASE2	ACTIVE_NOT_RECRUITING	Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Solid Tumors
NCT03866382	PHASE2	RECRUITING	Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
NCT04022343	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Cabozantinib in Treating Patients With Locally Advanced Kidney Cancer
NCT04071223	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, RadiCaL Study
NCT04258462	PHASE2	ACTIVE_NOT_RECRUITING	Hyperpolarized 13C Pyruvate MRI Scan in Predicting Tumor Aggressiveness in Patients With Renal Tumors
NCT04393350	PHASE2	ACTIVE_NOT_RECRUITING	Perioperative Lenvatinib With Pembrolizumab in Patients With Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma
NCT04969315	PHASE1/PHASE2	RECRUITING	TT-10 (PORT-6) and TT-4 (PORT-7) as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors
NCT04981509	PHASE2	RECRUITING	Testing of Bevacizumab, Erlotinib, and Atezolizumab in Combination for Advanced-Stage Kidney Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	18
SUNITINIB	4	15
SORAFENIB	4	13
PAZOPANIB	4	9
AXITINIB	4	6
ERLOTINIB	4	4
TIVOZANIB	4	4
NIVOLUMAB	4	3
TEMSIROLIMUS	4	3
VORINOSTAT	4	3
ZOLEDRONIC ACID ANHYDROUS	4	3
FLUDEOXYGLUCOSE F 18	4	2
INTERFERON ALFA-2A	4	2
IPILIMUMAB	4	2
LENVATINIB	4	2
AMIFOSTINE	4	1
AVELUMAB	4	1
BELZUTIFAN	4	1
CAFFEINE	4	1
CAPECITABINE	4	1
CRIZOTINIB	4	1
DACTINOMYCIN	4	1
DALTEPARIN SODIUM	4	1
ERIBULIN	4	1
INDOCYANINE GREEN	4	1
INDOCYANINE GREEN ACID FORM	4	1
INULIN	4	1
IRINOTECAN	4	1
ISOTRETINOIN	4	1
IXABEPILONE	4	1