Infiltrating bladder urothelial carcinoma

Summary

Infiltrating bladder urothelial carcinoma (MONDO:0003890) is a cancer (an umbrella term covering 9 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver) and 10 clinical trials. Molecularly, TSC1 Frameshift Truncation confers sensitivity to Everolimus in Invasive Bladder Transitional Cell Carcinoma (CIViC Level B). Top therapeutic interventions include cabozantinib, cabazitaxel, and tremelimumab.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 10
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	infiltrating bladder urothelial carcinoma
Mondo ID	MONDO:0003890
DOID	DOID:6477
NCIT	C27885
UMLS	C1334281
MedGen	233582
GARD	0023716
Is cancer (heuristic)	yes

Also known as: infiltrating bladder urothelial carcinoma · infiltrating transitional cell carcinoma of the urinary bladder · invasive bladder transitional cell carcinoma · invasive bladder urothelial carcinoma · invasive transitional cell carcinoma of the urinary bladder

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › urinary bladder disorder › urinary bladder neoplasm › urinary bladder cancer › urinary bladder carcinoma › bladder transitional cell carcinoma › infiltrating bladder urothelial carcinoma

Related subtypes (4): non-invasive bladder urothelial carcinoma, bladder papillary urothelial carcinoma, bladder urachal urothelial carcinoma, bladder sarcomatoid transitional cell carcinoma

Subtypes (9): infiltrating bladder urothelial carcinoma, clear cell variant, micropapillary variant infiltrating bladder urothelial carcinoma, infiltrating bladder urothelial carcinoma sarcomatoid variant, infiltrating bladder lymphoepithelioma-like carcinoma, lipid-cell variant infiltrating bladder urothelial carcinoma, plasmacytoid variant infiltrating bladder urothelial carcinoma, nested variant infiltrating bladder urothelial carcinoma, microcystic variant infiltrating bladder urothelial carcinoma, lymphoma-like variant infiltrating bladder urothelial 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: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TSC1	LoF	BLCA,BRCA,COADREAD,HCC,LUAD,RCC,SKCM,STAD,UTUC	CIViC #46

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex

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
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSC1	Other/Unknown	no		Hamartin

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
gluteal muscle	1
lateral globus pallidus	1
substantia nigra pars compacta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSC1	5,445

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSC1	Q92574	5

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
Inhibition of TSC complex formation by AKT (PKB)	1	2284.0×	0.002	TSC1
Energy dependent regulation of mTOR by LKB1-AMPK	1	393.8×	0.006	TSC1
TBC/RABGAPs	1	259.6×	0.006	TSC1
TP53 Regulates Metabolic Genes	1	129.8×	0.009	TSC1
Macroautophagy	1	115.3×	0.009	TSC1

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
memory T cell differentiation	1	5617.3×	0.004	TSC1
cellular response to decreased oxygen levels	1	4213.0×	0.004	TSC1
negative regulation of ATP-dependent activity	1	1685.2×	0.004	TSC1
negative regulation of cell size	1	1685.2×	0.004	TSC1
regulation of cell-matrix adhesion	1	1296.3×	0.004	TSC1
negative regulation of macroautophagy	1	1123.5×	0.004	TSC1
regulation of stress fiber assembly	1	991.3×	0.004	TSC1
obsolete D-glucose import	1	842.6×	0.004	TSC1
activation of GTPase activity	1	732.7×	0.004	TSC1
cardiac muscle cell differentiation	1	674.1×	0.004	TSC1
positive regulation of focal adhesion assembly	1	648.1×	0.004	TSC1
negative regulation of TOR signaling	1	561.7×	0.005	TSC1
associative learning	1	481.5×	0.005	TSC1
cell projection organization	1	374.5×	0.006	TSC1
negative regulation of TORC1 signaling	1	324.1×	0.006	TSC1
adult locomotory behavior	1	300.9×	0.006	TSC1
synapse organization	1	280.9×	0.006	TSC1
myelination	1	251.5×	0.007	TSC1
hippocampus development	1	230.8×	0.007	TSC1
response to insulin	1	230.8×	0.007	TSC1
cerebral cortex development	1	205.5×	0.007	TSC1
cellular response to starvation	1	193.7×	0.007	TSC1
potassium ion transport	1	191.5×	0.007	TSC1
neural tube closure	1	187.2×	0.007	TSC1
cell-matrix adhesion	1	163.6×	0.008	TSC1
kidney development	1	140.4×	0.008	TSC1
cell population proliferation	1	102.8×	0.011	TSC1
adaptive immune response	1	84.3×	0.013	TSC1
regulation of cell cycle	1	74.6×	0.014	TSC1
protein stabilization	1	66.9×	0.015	TSC1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TSC1

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)
TSC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	4
Not specified	4
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03609216	PHASE2	ACTIVE_NOT_RECRUITING	Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
NCT03866382	PHASE2	RECRUITING	Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
NCT01616875	PHASE2	COMPLETED	Bristol Bladder Trial
NCT03419130	PHASE2	WITHDRAWN	Radiation Therapy and Pembrolizumab in Treating Patients With Localized Urothelial Bladder Cancer
NCT03549715	PHASE1/PHASE2	UNKNOWN	NEoadjuvant Dose-dense MVAC In cOmbination With Durvalumab and Tremelimumab in Muscle-invasive Urothelial Carcinoma
NCT02767921	PHASE1	TERMINATED	sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer
NCT01495676	Not specified	TERMINATED	A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer
NCT02688348	Not specified	WITHDRAWN	Quality of Life After Bladder-Preservation Chemotherapy and Radiation Therapy in Patients With Muscle-Invasive Bladder Cancer
NCT02944357	Not specified	WITHDRAWN	Gemcitabine Hydrochloride, Cisplatin, and AGS-003-BLD in Treating Patients With Muscle-Invasive Bladder Cancer Undergoing Surgery
NCT03238664	Not specified	WITHDRAWN	Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	3
CABAZITAXEL	4	1
TREMELIMUMAB	4	1
SEPHB4-HSA	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
TSC1 Frameshift Truncation	Everolimus	Sensitivity/Response	CIViC B	EID320