Familial multiple meningioma

Summary

Familial multiple meningioma (MONDO:0016995) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial multiple meningioma
Mondo ID	MONDO:0016995
Orphanet	263662
ICD-11	160795085
UMLS	C4707361
MedGen	1644853
GARD	0017260
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › central nervous system neoplasm › tumor of meninges › familial multiple meningioma

Related subtypes (4): meningioma, diffuse leptomeningeal melanocytosis, malignant tumor of meninges, benign neoplasm of meninges

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3235266	NM_006767.4(LZTR1):c.102C>A (p.Cys34Ter)	LOC130067016	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
SMARCE1	Definitive	Autosomal dominant	familial meningioma	9
SMARCB1	Supportive	Autosomal dominant	familial multiple meningioma	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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

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
SMARCE1	HGNC:11109	ENSG00000073584	Q969G3	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	gencc

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).

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)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
SMARCE1	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf

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
embryo	2
ganglionic eminence	2
cortical plate	1
calcaneal tendon	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

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083
SMARCE1	2,977

Intra-cohort edges

A	B	Sources
SMARCB1	SMARCE1	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17
SMARCE1	Q969G3	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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×	2e-05	SMARCB1, SMARCE1
Formation of the polybromo-BAF (pBAF) complex	2	634.4×	2e-05	SMARCB1, SMARCE1
Formation of the embryonic stem cell BAF (esBAF) complex	2	601.0×	2e-05	SMARCB1, SMARCE1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	2	456.8×	2e-05	SMARCB1, SMARCE1
Regulation of endogenous retroelements	2	368.4×	3e-05	SMARCB1, SMARCE1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	2	300.5×	3e-05	SMARCB1, SMARCE1
Regulation of MITF-M-dependent genes involved in pigmentation	2	265.6×	4e-05	SMARCB1, SMARCE1
MITF-M-dependent gene expression	2	181.3×	7e-05	SMARCB1, SMARCE1
RMTs methylate histone arginines	2	146.4×	9e-05	SMARCB1, SMARCE1
Transcriptional regulation by RUNX1	2	146.4×	9e-05	SMARCB1, SMARCE1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	2	117.7×	1e-04	SMARCB1, SMARCE1
MITF-M-regulated melanocyte development	2	114.2×	1e-04	SMARCB1, SMARCE1
Chromatin organization	2	81.6×	2e-04	SMARCB1, SMARCE1
Chromatin modifying enzymes	2	72.3×	2e-04	SMARCB1, SMARCE1
Epigenetic regulation of gene expression	2	71.4×	2e-04	SMARCB1, SMARCE1
RNA Polymerase II Transcription	2	22.5×	0.002	SMARCB1, SMARCE1
Gene expression (Transcription)	2	17.8×	0.004	SMARCB1, SMARCE1
Generic Transcription Pathway	2	15.1×	0.005	SMARCB1, SMARCE1
Developmental Biology	2	14.5×	0.005	SMARCB1, SMARCE1

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
nucleosome disassembly	2	802.5×	2e-05	SMARCB1, SMARCE1
regulation of G0 to G1 transition	2	674.1×	2e-05	SMARCB1, SMARCE1
regulation of nucleotide-excision repair	2	601.9×	2e-05	SMARCB1, SMARCE1
regulation of mitotic metaphase/anaphase transition	2	495.6×	2e-05	SMARCB1, SMARCE1
positive regulation of T cell differentiation	2	455.5×	2e-05	SMARCB1, SMARCE1
positive regulation of myoblast differentiation	2	366.4×	3e-05	SMARCB1, SMARCE1
positive regulation of stem cell population maintenance	2	343.9×	3e-05	SMARCB1, SMARCE1
positive regulation of double-strand break repair	2	343.9×	3e-05	SMARCB1, SMARCE1
regulation of G1/S transition of mitotic cell cycle	2	306.4×	3e-05	SMARCB1, SMARCE1
positive regulation of cell differentiation	2	267.5×	4e-05	SMARCB1, SMARCE1
single stranded viral RNA replication via double stranded DNA intermediate	1	8426.0×	3e-04	SMARCB1
chromatin remodeling	2	73.0×	4e-04	SMARCB1, SMARCE1
positive regulation of glucose mediated signaling pathway	1	2808.7×	7e-04	SMARCB1
RNA polymerase I preinitiation complex assembly	1	1685.2×	0.001	SMARCB1
DNA integration	1	1053.2×	0.002	SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	766.0×	0.002	SMARCB1
hepatocyte differentiation	1	601.9×	0.003	SMARCB1
host-mediated activation of viral transcription	1	443.5×	0.003	SMARCB1
blastocyst hatching	1	271.8×	0.005	SMARCB1
transcription initiation-coupled chromatin remodeling	1	191.5×	0.007	SMARCB1
regulation of transcription by RNA polymerase II	2	11.7×	0.009	SMARCB1, SMARCE1
neurogenesis	1	104.0×	0.011	SMARCE1
nervous system development	1	23.0×	0.049	SMARCB1
negative regulation of cell population proliferation	1	21.1×	0.051	SMARCB1
negative regulation of DNA-templated transcription	1	15.8×	0.065	SMARCE1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	SMARCB1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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
SMARCB1	0	0
SMARCE1	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: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

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	2	SMARCB1, SMARCE1

Undrugged target profiles

2 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	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.