Renal pelvis urothelial carcinoma

Summary

Renal pelvis urothelial carcinoma (MONDO:0005221) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 15 clinical trials. Molecularly, FGFR3 S249C confers sensitivity to AZD-4547 in Renal Pelvis Transitional Cell Carcinoma (CIViC Level C); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include cabozantinib, avelumab, and atezolizumab.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 15
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal pelvis urothelial carcinoma
Mondo ID	MONDO:0005221
EFO	EFO:0003017
DOID	DOID:5974
NCIT	C7355
SNOMED CT	408642003
UMLS	C4087468
MedGen	1648131
GARD	0024167
Anatomy (UBERON)	UBERON:0001224
Is cancer (heuristic)	yes

Also known as: kidney renal pelvis urothelial cancer · renal pelvis transitional cell carcinoma · renal pelvis urothelial cancer · renal pelvis urothelial carcinoma · transitional cell carcinoma of renal pelvis · transitional cell carcinoma of the renal pelvis · urothelial cell carcinoma of renal pelvis · urothelial cell carcinoma of the renal pelvis

Data availability: 4 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › malignant urinary system neoplasm › kidney cancer › renal carcinoma › renal pelvis carcinoma › renal pelvis urothelial carcinoma

Related subtypes (3): renal pelvis adenocarcinoma, renal pelvis squamous cell carcinoma, carcinoma in situ of renal pelvis

Subtypes (3): infiltrating renal pelvis transitional cell carcinoma, renal pelvis papillary urothelial carcinoma, kidney pelvis sarcomatoid transitional 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2

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
skin of hip	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR3	4,510

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR3	P22607	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
t(4;14) translocations of FGFR3	1	11420.0×	7e-04	FGFR3
Signaling by FGFR3 fusions in cancer	1	11420.0×	7e-04	FGFR3
FGFR3b ligand binding and activation	1	1631.4×	0.003	FGFR3
Signaling by activated point mutants of FGFR3	1	951.7×	0.003	FGFR3
FGFR3c ligand binding and activation	1	878.5×	0.003	FGFR3
Phospholipase C-mediated cascade; FGFR3	1	878.5×	0.003	FGFR3
PI-3K cascade:FGFR3	1	634.4×	0.003	FGFR3
SHC-mediated cascade:FGFR3	1	601.0×	0.003	FGFR3
FRS-mediated FGFR3 signaling	1	543.8×	0.003	FGFR3
Signaling by FGFR3 in disease	1	496.5×	0.003	FGFR3
Negative regulation of FGFR3 signaling	1	439.2×	0.003	FGFR3
PI3K Cascade	1	271.9×	0.005	FGFR3
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.010	FGFR3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	FGFR3
PIP3 activates AKT signaling	1	66.8×	0.016	FGFR3
RAF/MAP kinase cascade	1	61.1×	0.016	FGFR3

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
negative regulation of developmental growth	1	16852.0×	0.001	FGFR3
fibroblast growth factor receptor apoptotic signaling pathway	1	8426.0×	0.001	FGFR3
bone maturation	1	5617.3×	0.001	FGFR3
positive regulation of phospholipase activity	1	3370.4×	0.001	FGFR3
endochondral bone growth	1	1685.2×	0.002	FGFR3
chondrocyte proliferation	1	1053.2×	0.003	FGFR3
positive regulation of tyrosine phosphorylation of STAT protein	1	732.7×	0.004	FGFR3
bone morphogenesis	1	601.9×	0.004	FGFR3
endochondral ossification	1	543.6×	0.004	FGFR3
chondrocyte differentiation	1	300.9×	0.006	FGFR3
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.006	FGFR3
fibroblast growth factor receptor signaling pathway	1	285.6×	0.006	FGFR3
bone mineralization	1	271.8×	0.006	FGFR3
MAPK cascade	1	153.2×	0.009	FGFR3
skeletal system development	1	125.8×	0.011	FGFR3
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.014	FGFR3
positive regulation of MAPK cascade	1	80.6×	0.014	FGFR3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.014	FGFR3
cell-cell signaling	1	69.6×	0.015	FGFR3
positive regulation of cell population proliferation	1	33.6×	0.030	FGFR3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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.

Symbol	Example approved molecule
FGFR3	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR3	64	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3
FORETINIB	2	FGFR3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR3	975	Binding:948, Functional:18, ADMET:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR3	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR3	975

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

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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3
FORETINIB	2	FGFR3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FGFR3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 15.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	7
PHASE3	4
PHASE1	2
EARLY_PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04637594	PHASE3	ACTIVE_NOT_RECRUITING	Trying to Find the Correct Length of Treatment With Immune Checkpoint Therapy
NCT05092958	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study
NCT00942331	PHASE3	COMPLETED	Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer
NCT02793128	PHASE3	COMPLETED	The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study
NCT03237780	PHASE2	ACTIVE_NOT_RECRUITING	Atezolizumab With or Without Eribulin Mesylate in Treating Patients With Recurrent Locally Advanced or Metastatic Urothelial Cancer
NCT04848519	PHASE2	ACTIVE_NOT_RECRUITING	Immune Checkpoint Inhibitors With or Without Propranolol Hydrochloride In Patients With Urothelial Carcinoma
NCT04940299	PHASE2	ACTIVE_NOT_RECRUITING	Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma
NCT04953104	PHASE2	ACTIVE_NOT_RECRUITING	ARID1A and/or KDM6A Mutation and CXCL13 Expression
NCT00749892	PHASE2	COMPLETED	Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer
NCT03513952	PHASE2	COMPLETED	Atezolizumab and CYT107 in Treating Participants With Locally Advanced, Inoperable, or Metastatic Urothelial Carcinoma
NCT03935347	PHASE2	WITHDRAWN	Adoptive Cell Therapy With (LN-145) in Combination With Pembrolizumab in Treating Patients With Unresectable or Metastatic Transitional Cell Cancer Who Have Failed Cisplatin-Based Chemotherapy
NCT02496208	PHASE1	ACTIVE_NOT_RECRUITING	Cabozantinib S-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors
NCT04963153	PHASE1	ACTIVE_NOT_RECRUITING	Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
NCT02812420	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery
NCT05874921	Not specified	RECRUITING	uTRACT Jelmyto Registry: A Registry of Patients With Upper Tract Urothelial Cancer (UTUC) Treated With Jelmyto

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	4
AVELUMAB	4	2
ATEZOLIZUMAB	4	1
CISPLATIN	4	1
DURVALUMAB	4	1
ENFORTUMAB VEDOTIN	4	1
ERDAFITINIB	4	1
ERIBULIN MESYLATE	4	1
GEMCITABINE HYDROCHLORIDE	4	1
LIFILEUCEL	4	1
MITOMYCIN	4	1
RELATLIMAB	4	1
CHEMBL5412235	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
FGFR3 S249C	AZD-4547	Sensitivity/Response	CIViC C	EID8316
FGFR3::TACC3 Fusion	Fexagratinib	Sensitivity/Response	CIViC C	EID9227