Ureter small cell carcinoma

Summary

Ureter small cell carcinoma (MONDO:0006482) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 1 clinical trial. Molecularly, RAD50 L1237F confers sensitivity to Irinotecan + Checkpoint Kinase Inhibitor AZD7762 in Ureter Small Cell Carcinoma (CIViC Level C). Top therapeutic interventions include cisplatin.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 1
• 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	ureter small cell carcinoma
Mondo ID	MONDO:0006482
DOID	DOID:6886
NCIT	C6176
UMLS	C1336878
MedGen	234971
GARD	0024430
Anatomy (UBERON)	UBERON:0000056
Is cancer (heuristic)	yes

Also known as: small cell carcinoma of the ureter · small cell carcinoma of ureter · ureter small cell carcinoma · ureteral small cell carcinoma

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › neuroendocrine carcinoma › small cell carcinoma › ureter small cell carcinoma

Related subtypes (17): extrahepatic bile duct small cell adenocarcinoma, ovarian small cell carcinoma, colon small cell neuroendocrine carcinoma, urinary bladder small cell neuroendocrine carcinoma, esophageal small cell neuroendocrine carcinoma, ampulla of vater small cell neuroendocrine carcinoma, Bartholin gland small cell carcinoma, thymus small cell carcinoma, cervical small cell carcinoma, endometrial small cell carcinoma, gallbladder small cell neuroendocrine carcinoma, gastric small cell neuroendocrine carcinoma, laryngeal small cell carcinoma, pancreatic small cell neuroendocrine carcinoma, prostate small cell carcinoma, salivary gland small cell carcinoma, small cell lung 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: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RAD50	Act	GBM	CIViC #8032

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAD50	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD50	Orphanet:240760	Nijmegen breakage syndrome-like disorder

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
RAD50	HGNC:9816	ENSG00000113522	Q92878	DNA repair protein RAD50	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAD50	DNA repair protein RAD50	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

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)
RAD50	Other/Unknown	no		Rad50_eukaryotes, Zn_hook_RAD50, P-loop_NTPase

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
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAD50	134	ubiquitous	marker	corpus callosum, calcaneal tendon, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAD50	2,552

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAD50	Q92878	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Sensing of DNA Double Strand Breaks	1	1903.3×	0.006	RAD50
HDR through MMEJ (alt-NHEJ)	1	878.5×	0.006	RAD50
Impaired BRCA2 binding to PALB2	1	456.8×	0.006	RAD50
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.006	RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.006	RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.006	RAD50
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.006	RAD50
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.006	RAD50
Impaired BRCA2 binding to RAD51	1	308.6×	0.006	RAD50
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.006	RAD50
HDR through Single Strand Annealing (SSA)	1	292.8×	0.006	RAD50
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.006	RAD50
HDR through Homologous Recombination (HRR)	1	190.3×	0.008	RAD50
Nonhomologous End-Joining (NHEJ)	1	167.9×	0.008	RAD50
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.008	RAD50
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.008	RAD50
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.008	RAD50
Meiotic recombination	1	129.8×	0.009	RAD50
G2/M DNA damage checkpoint	1	120.2×	0.009	RAD50
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.009	RAD50
Processing of DNA double-strand break ends	1	114.2×	0.009	RAD50

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
regulation of mitotic recombination	1	8426.0×	0.001	RAD50
telomeric 3’ overhang formation	1	4213.0×	0.001	RAD50
chromosome organization involved in meiotic cell cycle	1	3370.4×	0.001	RAD50
negative regulation of telomere capping	1	3370.4×	0.001	RAD50
DNA strand resection involved in replication fork processing	1	2106.5×	0.002	RAD50
R-loop processing	1	1685.2×	0.002	RAD50
telomere maintenance via recombination	1	1532.0×	0.002	RAD50
DNA double-strand break processing	1	1532.0×	0.002	RAD50
homologous recombination	1	1404.3×	0.002	RAD50
mitotic G2/M transition checkpoint	1	802.5×	0.002	RAD50
telomere maintenance via telomerase	1	732.7×	0.002	RAD50
reciprocal meiotic recombination	1	561.7×	0.003	RAD50
positive regulation of telomere maintenance	1	510.7×	0.003	RAD50
positive regulation of double-strand break repair	1	343.9×	0.004	RAD50
DNA recombination	1	337.0×	0.004	RAD50
telomere maintenance	1	267.5×	0.005	RAD50
double-strand break repair	1	203.0×	0.006	RAD50
double-strand break repair via homologous recombination	1	156.0×	0.007	RAD50
DNA repair	1	63.8×	0.016	RAD50
DNA damage response	1	53.5×	0.019	RAD50

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAD50	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	RAD50

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RAD50	7	Binding:7

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

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	RAD50

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	RAD50
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03582475	PHASE1	ACTIVE_NOT_RECRUITING	Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	1

Precision-medicine subtype map (CIViC)

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

Molecular subtype	Therapy	Effect	Level	CIViC
RAD50 L1237F	Irinotecan + Checkpoint Kinase Inhibitor AZD7762	Sensitivity/Response	CIViC C	EID5829