Kidney medullary carcinoma

Summary

Kidney medullary carcinoma (MONDO:0006260) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 18 clinical trials. Top therapeutic interventions include cabozantinib, tazemetostat, and enfortumab vedotin.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• Clinical trials: 18

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000		Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	kidney medullary carcinoma
Mondo ID	MONDO:0006260
EFO	EFO:1000314
Orphanet	319319
DOID	DOID:0070475
NCIT	C7572
UMLS	C4049328
MedGen	888108
GARD	0013175
MedDRA	10064886
NORD	1999
Anatomy (UBERON)	UBERON:0000362
Is cancer (heuristic)	yes

Also known as: carcinoma of renal medulla · kidney medullary carcinoma · renal medulla carcinoma · Renal Medullary Carcinoma · renal medullary carcinoma

Data availability: 9 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 › carcinoma › adenocarcinoma › renal cell carcinoma › kidney medullary carcinoma

Related subtypes (10): mucinous tubular and spindle renal cell carcinoma, renal pelvis adenocarcinoma, Wolffian duct adenocarcinoma, collecting duct carcinoma, renal cell adenocarcinoma, cystic renal cell carcinoma, adrenal cortex carcinoma, nonpapillary renal cell carcinoma, MIT family translocation renal cell carcinoma, acquired cystic disease-associated renal cell carcinoma

Subtypes (1): SMARCB1-deficient kidney medullary 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: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMARCB1	Act	ATRT,MBL,NBL,PANET,PAST	CIViC #5356

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCB1	Orphanet:1465	Coffin-Siris syndrome
SMARCB1	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCB1	Orphanet:2495	Meningioma
SMARCB1	Orphanet:263662	Familial multiple meningioma
SMARCB1	Orphanet:93921	Full schwannomatosis
SMARCB1	Orphanet:99966	Atypical teratoid rhabdoid tumor

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
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.

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)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd

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
cortical plate	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.010	SMARCB1
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.010	SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.010	SMARCB1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.010	SMARCB1
Regulation of endogenous retroelements	1	368.4×	0.010	SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.010	SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.010	SMARCB1
MITF-M-dependent gene expression	1	181.3×	0.013	SMARCB1
RMTs methylate histone arginines	1	146.4×	0.013	SMARCB1
Transcriptional regulation by RUNX1	1	146.4×	0.013	SMARCB1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	SMARCB1
MITF-M-regulated melanocyte development	1	114.2×	0.014	SMARCB1
Chromatin organization	1	81.6×	0.018	SMARCB1
Chromatin modifying enzymes	1	72.3×	0.018	SMARCB1
Epigenetic regulation of gene expression	1	71.4×	0.018	SMARCB1
RNA Polymerase II Transcription	1	22.5×	0.053	SMARCB1
Gene expression (Transcription)	1	17.8×	0.063	SMARCB1
Generic Transcription Pathway	1	15.1×	0.069	SMARCB1
Developmental Biology	1	14.5×	0.069	SMARCB1

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
single stranded viral RNA replication via double stranded DNA intermediate	1	16852.0×	0.001	SMARCB1
positive regulation of glucose mediated signaling pathway	1	5617.3×	0.002	SMARCB1
RNA polymerase I preinitiation complex assembly	1	3370.4×	0.002	SMARCB1
DNA integration	1	2106.5×	0.003	SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	1532.0×	0.003	SMARCB1
hepatocyte differentiation	1	1203.7×	0.003	SMARCB1
host-mediated activation of viral transcription	1	887.0×	0.004	SMARCB1
nucleosome disassembly	1	802.5×	0.004	SMARCB1
regulation of G0 to G1 transition	1	674.1×	0.004	SMARCB1
regulation of nucleotide-excision repair	1	601.9×	0.004	SMARCB1
blastocyst hatching	1	543.6×	0.004	SMARCB1
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	SMARCB1
positive regulation of T cell differentiation	1	455.5×	0.004	SMARCB1
transcription initiation-coupled chromatin remodeling	1	383.0×	0.004	SMARCB1
positive regulation of myoblast differentiation	1	366.4×	0.004	SMARCB1
positive regulation of stem cell population maintenance	1	343.9×	0.004	SMARCB1
positive regulation of double-strand break repair	1	343.9×	0.004	SMARCB1
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.004	SMARCB1
positive regulation of cell differentiation	1	267.5×	0.005	SMARCB1
chromatin remodeling	1	73.0×	0.016	SMARCB1
nervous system development	1	45.9×	0.025	SMARCB1
negative regulation of cell population proliferation	1	42.1×	0.026	SMARCB1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	SMARCB1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	SMARCB1

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
SMARCB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCB1	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

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	SMARCB1

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)
SMARCB1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 18.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	10
PHASE1/PHASE2	3
Not specified	3
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02721732	PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic
NCT03587662	PHASE2	ACTIVE_NOT_RECRUITING	Ixazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
NCT03866382	PHASE2	RECRUITING	Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
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
NCT05286801	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
NCT05347212	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Trial of Immunotherapy in Patients With Carcinomas Arising From the Renal Medulla
NCT06161532	PHASE2	RECRUITING	Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as High Grade Neuroendocrine Carcinomas, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile C…
NCT06302569	PHASE2	RECRUITING	Pembrolizumab Plus Enfortumab Vedotin in Collecting Duct and Renal Medullary Carcinoma
NCT00027820	PHASE1/PHASE2	COMPLETED	Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer
NCT01767636	PHASE2	COMPLETED	Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer
NCT02601950	PHASE2	COMPLETED	A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
NCT02875548	PHASE1/PHASE2	COMPLETED	A Study to Assess Long-term Safety of Tazemetostat in Adult Participants of All Ages With Any Disease Treated With Tazemetostat in a Previous Clinical Study
NCT03274258	PHASE2	TERMINATED	Phase II Trial of Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma
NCT02496208	PHASE1	ACTIVE_NOT_RECRUITING	Cabozantinib S-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary Tumors
NCT04537715	PHASE1	COMPLETED	Effects of Itraconazole and Rifampin on the Blood Tazemetostat Levels
NCT07502716	Not specified	AVAILABLE	Compassionate Use of Ubamatamab
NCT00898365	Not specified	COMPLETED	Study of Kidney Tumors in Younger Patients
NCT03874455	Not specified	NO_LONGER_AVAILABLE	Tazemetostat Expanded Access Program for Adults With Solid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	5
TAZEMETOSTAT	4	4
ENFORTUMAB VEDOTIN	4	1
FLUDARABINE PHOSPHATE	4	1
FLUDEOXYGLUCOSE F 18	4	1
IXAZOMIB CITRATE	4	1
PAZOPANIB HYDROCHLORIDE	4	1
RADIUM RA 223 DICHLORIDE	4	1
RELATLIMAB	4	1
SACITUZUMAB GOVITECAN	4	1
IXAZOMIB	3	1
TIRAGOLUMAB	3	1
UBAMATAMAB	2	1
CHEMBL5398431	0	4
CHEMBL1813256	0	1