Familial rhabdoid tumor

Summary

Familial rhabdoid tumor (MONDO:0016473) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers) and 1 clinical trial.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial rhabdoid tumor
Mondo ID	MONDO:0016473
OMIM	609322
Orphanet	231108
DOID	DOID:0070617
NCIT	C93268
UMLS	C2985524
MedGen	457750
GARD	0017159
Is cancer (heuristic)	yes

Also known as: familial posterior fossa brain tumor syndrome of infancy · familial posterior fossa brain tumour syndrome of infancy · familial rhabdoid tumor · hereditary rhabdoid tumor · hereditary rhabdoid tumour · rhabdoid predisposition syndrome · rhabdoid tumor predisposition syndrome · rhabdoid tumour predisposition syndrome · RTPS

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › embryonal neoplasm › rhabdoid tumor › familial rhabdoid tumor

Related subtypes (4): striated muscle rhabdoid tumor, rhabdoid tumor of the kidney, atypical teratoid rhabdoid tumor, extrarenal rhabdoid tumor

Subtypes (2): rhabdoid tumor predisposition syndrome 1, rhabdoid tumor predisposition syndrome 2

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: 30 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
SMARCB1	Act	ATRT,MBL,NBL,PANET,PAST	CIViC #5356

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SMARCA4	Definitive	Autosomal dominant	rhabdoid tumor predisposition syndrome 2	14
SMARCB1	Definitive	Autosomal dominant	rhabdoid tumor predisposition syndrome 1	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	gencc
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
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: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	2
ganglionic eminence	2
cervix squamous epithelium	1
embryo	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA4	8,138
SMARCB1	5,083

Intra-cohort edges

A	B	Sources
SMARCA4	SMARCB1	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCA4	P51532	31
SMARCB1	Q12824	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	634.4×	3e-05	SMARCA4, SMARCB1
Formation of the polybromo-BAF (pBAF) complex	2	634.4×	3e-05	SMARCA4, SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	2	601.0×	3e-05	SMARCA4, SMARCB1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	2	456.8×	4e-05	SMARCA4, SMARCB1
Regulation of endogenous retroelements	2	368.4×	5e-05	SMARCA4, SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	2	300.5×	6e-05	SMARCA4, SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	2	265.6×	6e-05	SMARCA4, SMARCB1
MITF-M-dependent gene expression	2	181.3×	1e-04	SMARCA4, SMARCB1
RMTs methylate histone arginines	2	146.4×	1e-04	SMARCA4, SMARCB1
Transcriptional regulation by RUNX1	2	146.4×	1e-04	SMARCA4, SMARCB1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	2	117.7×	2e-04	SMARCA4, SMARCB1
MITF-M-regulated melanocyte development	2	114.2×	2e-04	SMARCA4, SMARCB1
Chromatin organization	2	81.6×	4e-04	SMARCA4, SMARCB1
Chromatin modifying enzymes	2	72.3×	4e-04	SMARCA4, SMARCB1
Epigenetic regulation of gene expression	2	71.4×	4e-04	SMARCA4, SMARCB1
RNA Polymerase II Transcription	2	22.5×	0.004	SMARCA4, SMARCB1
Formation of the non-canonical BAF (ncBAF) complex	1	335.9×	0.006	SMARCA4
Gene expression (Transcription)	2	17.8×	0.006	SMARCA4, SMARCB1
Generic Transcription Pathway	2	15.1×	0.007	SMARCA4, SMARCB1
Developmental Biology	2	14.5×	0.008	SMARCA4, SMARCB1
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.008	SMARCA4
Interleukin-7 signaling	1	158.6×	0.009	SMARCA4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.019	SMARCA4
Formation of the beta-catenin:TCF transactivating complex	1	60.1×	0.021	SMARCA4
Negative Regulation of CDH1 Gene Transcription	1	60.1×	0.021	SMARCA4
TCF dependent signaling in response to WNT	1	58.9×	0.021	SMARCA4
Signaling by WNT	1	56.0×	0.021	SMARCA4
Signaling by Interleukins	1	32.1×	0.035	SMARCA4
Nervous system development	1	21.5×	0.051	SMARCA4
Cytokine Signaling in Immune system	1	20.4×	0.052	SMARCA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 glucose mediated signaling pathway	2	5617.3×	8e-07	SMARCA4, SMARCB1
RNA polymerase I preinitiation complex assembly	2	3370.4×	1e-06	SMARCA4, SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	2	1532.0×	5e-06	SMARCA4, SMARCB1
host-mediated activation of viral transcription	2	887.0×	1e-05	SMARCA4, SMARCB1
nucleosome disassembly	2	802.5×	1e-05	SMARCA4, SMARCB1
regulation of G0 to G1 transition	2	674.1×	1e-05	SMARCA4, SMARCB1
regulation of nucleotide-excision repair	2	601.9×	1e-05	SMARCA4, SMARCB1
regulation of mitotic metaphase/anaphase transition	2	495.6×	2e-05	SMARCA4, SMARCB1
positive regulation of T cell differentiation	2	455.5×	2e-05	SMARCA4, SMARCB1
transcription initiation-coupled chromatin remodeling	2	383.0×	2e-05	SMARCA4, SMARCB1
positive regulation of myoblast differentiation	2	366.4×	2e-05	SMARCA4, SMARCB1
positive regulation of stem cell population maintenance	2	343.9×	2e-05	SMARCA4, SMARCB1
positive regulation of double-strand break repair	2	343.9×	2e-05	SMARCA4, SMARCB1
regulation of G1/S transition of mitotic cell cycle	2	306.4×	3e-05	SMARCA4, SMARCB1
positive regulation of cell differentiation	2	267.5×	3e-05	SMARCA4, SMARCB1
single stranded viral RNA replication via double stranded DNA intermediate	1	8426.0×	3e-04	SMARCB1
chromatin remodeling	2	73.0×	4e-04	SMARCA4, SMARCB1
nervous system development	2	45.9×	1e-03	SMARCA4, SMARCB1
DNA integration	1	1053.2×	0.002	SMARCB1
hepatocyte differentiation	1	601.9×	0.003	SMARCB1
positive regulation of signal transduction by p53 class mediator	1	601.9×	0.003	SMARCA4
neural retina development	1	468.1×	0.003	SMARCA4
negative regulation of androgen receptor signaling pathway	1	468.1×	0.003	SMARCA4
blastocyst hatching	1	271.8×	0.006	SMARCB1
positive regulation of transcription by RNA polymerase II	2	14.9×	0.007	SMARCA4, SMARCB1
positive regulation of Wnt signaling pathway	1	191.5×	0.007	SMARCA4
positive regulation of miRNA transcription	1	145.3×	0.009	SMARCA4
negative regulation of cell differentiation	1	142.8×	0.009	SMARCA4
regulation of transcription by RNA polymerase II	2	11.7×	0.009	SMARCA4, SMARCB1
heterochromatin formation	1	127.7×	0.010	SMARCA4

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
SMARCA4	2	2
SMARCB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMARCA4
CAMIBIRSTAT	2	SMARCA4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCA4	230	Binding:207, ADMET:12, Functional:11
SMARCB1	7	Binding:7

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA4	230

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

2 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	SMARCA4
CAMIBIRSTAT	2	SMARCA4

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	SMARCA4
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	SMARCA4

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition