Rhabdoid tumor predisposition syndrome 1

Summary

Rhabdoid tumor predisposition syndrome 1 (MONDO:0012252) is a cancer caused by SMARCB1 (GenCC Definitive), with 3 cohort genes (1 CIViC-evidence somatic driver; 92 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Causal gene: SMARCB1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 92

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rhabdoid tumor predisposition syndrome 1
Mondo ID	MONDO:0012252
MeSH	C563738
OMIM	609322
DOID	DOID:0070618
NCIT	C178393
UMLS	C1836327
MedGen	322892
GARD	0018318
Is cancer (heuristic)	yes

Also known as: familial rhabdoid tumor caused by mutation in SMARCB1 · familial rhabdoid tumour caused by mutation in SMARCB1 · rhabdoid tumor predisposition syndrome 1 · rhabdoid tumor predisposition syndrome type 1 · rhabdoid tumors, somatic · rhabdoid tumour predisposition syndrome type 1 · RTPS1 · SMARCB1 familial rhabdoid tumor · SMARCB1 familial rhabdoid tumour

Data availability: 92 ClinVar variants · 5 GenCC gene-disease records.

Disease family

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 › rhabdoid tumor predisposition syndrome 1

Related subtypes (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

ClinVar germline variants

92 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 15 conflicting classifications of pathogenicity, 14 pathogenic, 12 benign/likely benign, 5 benign, 3 likely benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032872	NM_003073.5(SMARCB1):c.1062_1063del (p.Glu354fs)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1416806	NM_003073.5(SMARCB1):c.1148del (p.Pro383fs)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1803243	NM_003073.5(SMARCB1):c.575_584dup (p.Asp196fs)	SMARCB1	Pathogenic	criteria provided, single submitter
30201	NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
3602708	NM_003073.5(SMARCB1):c.40_46dup (p.Lys16fs)	SMARCB1	Pathogenic	criteria provided, single submitter
4056242	NM_003073.5(SMARCB1):c.592C>T (p.Gln198Ter)	SMARCB1	Pathogenic	criteria provided, single submitter
410698	NM_003073.5(SMARCB1):c.118C>T (p.Arg40Ter)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
464313	NC_000022.11:g.(?23787164)(23834186_?)del	SMARCB1	Pathogenic	criteria provided, single submitter
464316	NC_000022.11:g.(?23793553)(23793694_?)del	SMARCB1	Pathogenic	criteria provided, single submitter
464323	NM_003073.5(SMARCB1):c.184A>T (p.Lys62Ter)	SMARCB1	Pathogenic	criteria provided, single submitter
695025	NM_003073.5(SMARCB1):c.812del (p.Gly271fs)	SMARCB1	Pathogenic	criteria provided, single submitter
8024	NM_003073.5(SMARCB1):c.591del (p.Gln198fs)	SMARCB1	Pathogenic	no assertion criteria provided
8030	NM_003073.5(SMARCB1):c.629-361_795+2103dup	SMARCB1	Pathogenic	no assertion criteria provided
995897	NM_003073.5(SMARCB1):c.472C>T (p.Arg158Ter)	SMARCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
532988	NC_000022.11:g.(?23833566)(23834186_?)del	SMARCB1	Likely pathogenic	criteria provided, single submitter
8025	NM_003073.5(SMARCB1):c.986+1G>A	SMARCB1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
135257	NM_003073.5(SMARCB1):c.1A>G (p.Met1Val)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3240535	NM_003073.5(SMARCB1):c.1102C>T (p.Gln368Ter)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340912	NM_003073.5(SMARCB1):c.607G>A (p.Ala203Thr)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340913	NM_003073.5(SMARCB1):c.628+13C>T	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340915	NM_003073.5(SMARCB1):c.987-4G>C	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
340918	NM_003073.5(SMARCB1):c.*17C>T	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464334	NM_003073.5(SMARCB1):c.695C>T (p.Thr232Met)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464337	NM_003073.5(SMARCB1):c.749C>T (p.Thr250Met)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532969	NM_003073.5(SMARCB1):c.1ATG[3] (p.Met4del)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532973	NM_003073.5(SMARCB1):c.169G>A (p.Val57Met)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
532975	NM_003073.5(SMARCB1):c.309C>T (p.Asn103=)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
580688	NM_003073.5(SMARCB1):c.790A>G (p.Ile264Val)	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
826292	NM_003073.5(SMARCB1):c.628+4C>T	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827354	NM_003073.5(SMARCB1):c.795+5G>A	SMARCB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 9 · 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

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
SMARCB1	Definitive	Autosomal dominant	rhabdoid tumor predisposition syndrome 1	16

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
SMARCE1	Orphanet:1465	Coffin-Siris syndrome
SMARCE1	Orphanet:2495	Meningioma
SMARCE1	Orphanet:263662	Familial multiple meningioma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

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	gencc,clinvar
SMARCE1	HGNC:11109	ENSG00000073584	Q969G3	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	clinvar
DERL3	HGNC:14236	ENSG00000099958	Q96Q80	Derlin-3	clinvar

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.
SMARCE1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
DERL3	Derlin-3	Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
SMARCE1	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf
DERL3	Other/Unknown	no		DER1, Rhomboid-like_sf

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
embryo	2
ganglionic eminence	2
cortical plate	1
calcaneal tendon	1
bone marrow cell	1
duodenum	1
tonsil	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate
SMARCE1	197	ubiquitous	marker	calcaneal tendon, embryo, ganglionic eminence
DERL3	135	ubiquitous	marker	bone marrow cell, duodenum, tonsil

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083
SMARCE1	2,977
DERL3	1,156

Intra-cohort edges

A	B	Sources
SMARCB1	SMARCE1	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17
SMARCE1	Q969G3	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DERL3	Q96Q80	84.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 3 evidence-associated genes (3 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 3 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	423.0×	6e-05	SMARCB1, SMARCE1
Formation of the polybromo-BAF (pBAF) complex	2	423.0×	6e-05	SMARCB1, SMARCE1
Formation of the embryonic stem cell BAF (esBAF) complex	2	400.7×	6e-05	SMARCB1, SMARCE1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	2	304.5×	8e-05	SMARCB1, SMARCE1
Regulation of endogenous retroelements	2	245.6×	9e-05	SMARCB1, SMARCE1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	2	200.3×	1e-04	SMARCB1, SMARCE1
Regulation of MITF-M-dependent genes involved in pigmentation	2	177.1×	1e-04	SMARCB1, SMARCE1
MITF-M-dependent gene expression	2	120.8×	2e-04	SMARCB1, SMARCE1
RMTs methylate histone arginines	2	97.6×	3e-04	SMARCB1, SMARCE1
Transcriptional regulation by RUNX1	2	97.6×	3e-04	SMARCB1, SMARCE1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	2	78.5×	4e-04	SMARCB1, SMARCE1
MITF-M-regulated melanocyte development	2	76.1×	4e-04	SMARCB1, SMARCE1
Chromatin organization	2	54.4×	8e-04	SMARCB1, SMARCE1
Chromatin modifying enzymes	2	48.2×	9e-04	SMARCB1, SMARCE1
Epigenetic regulation of gene expression	2	47.6×	9e-04	SMARCB1, SMARCE1
RNA Polymerase II Transcription	2	15.0×	0.008	SMARCB1, SMARCE1
Gene expression (Transcription)	2	11.9×	0.012	SMARCB1, SMARCE1
Defective CFTR causes cystic fibrosis	1	73.2×	0.015	DERL3
Generic Transcription Pathway	2	10.1×	0.015	SMARCB1, SMARCE1
Developmental Biology	2	9.6×	0.015	SMARCB1, SMARCE1
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	1	64.5×	0.016	DERL3
ABC-family protein mediated transport	1	40.5×	0.024	DERL3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nucleosome disassembly	2	535.0×	8e-05	SMARCB1, SMARCE1
regulation of G0 to G1 transition	2	449.4×	8e-05	SMARCB1, SMARCE1
regulation of nucleotide-excision repair	2	401.2×	8e-05	SMARCB1, SMARCE1
regulation of mitotic metaphase/anaphase transition	2	330.4×	8e-05	SMARCB1, SMARCE1
positive regulation of T cell differentiation	2	303.6×	8e-05	SMARCB1, SMARCE1
positive regulation of myoblast differentiation	2	244.2×	9e-05	SMARCB1, SMARCE1
positive regulation of stem cell population maintenance	2	229.3×	9e-05	SMARCB1, SMARCE1
positive regulation of double-strand break repair	2	229.3×	9e-05	SMARCB1, SMARCE1
regulation of G1/S transition of mitotic cell cycle	2	204.3×	1e-04	SMARCB1, SMARCE1
positive regulation of cell differentiation	2	178.3×	1e-04	SMARCB1, SMARCE1
single stranded viral RNA replication via double stranded DNA intermediate	1	5617.3×	5e-04	SMARCB1
positive regulation of glucose mediated signaling pathway	1	1872.4×	0.001	SMARCB1
chromatin remodeling	2	48.6×	0.001	SMARCB1, SMARCE1
RNA polymerase I preinitiation complex assembly	1	1123.5×	0.002	SMARCB1
DNA integration	1	702.2×	0.003	SMARCB1
negative regulation of retrograde protein transport, ER to cytosol	1	624.1×	0.003	DERL3
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	510.7×	0.003	SMARCB1
hepatocyte differentiation	1	401.2×	0.004	SMARCB1
host-mediated activation of viral transcription	1	295.6×	0.005	SMARCB1
obsolete protein N-linked glycosylation via asparagine	1	224.7×	0.007	DERL3
blastocyst hatching	1	181.2×	0.008	SMARCB1
transcription initiation-coupled chromatin remodeling	1	127.7×	0.011	SMARCB1
endoplasmic reticulum unfolded protein response	1	98.5×	0.013	DERL3
neurogenesis	1	69.3×	0.018	SMARCE1
ERAD pathway	1	60.4×	0.020	DERL3
regulation of transcription by RNA polymerase II	2	7.8×	0.024	SMARCB1, SMARCE1
nervous system development	1	15.3×	0.071	SMARCB1
negative regulation of cell population proliferation	1	14.0×	0.075	SMARCB1
negative regulation of DNA-templated transcription	1	10.5×	0.095	SMARCE1
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	SMARCB1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
SMARCE1	0	0
DERL3	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
SMARCE1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	SMARCB1, SMARCE1, DERL3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMARCB1	7	—
SMARCE1	7	—
DERL3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.