astroblastoma, MN1-altered

Summary

astroblastoma, MN1-altered (MONDO:0850349) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	astroblastoma, MN1-altered
Mondo ID	MONDO:0850349
DOID	DOID:0080904
GARD	0026609
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › glioma › astroblastoma › astroblastoma, MN1-altered

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
127446	NM_000051.4(ATM):c.7475T>G (p.Leu2492Arg)	ATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
647482	NM_000548.5(TSC2):c.5134G>A (p.Ala1712Thr)	TSC2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MN1	Orphanet:263662	Familial multiple meningioma
MN1	Orphanet:693549	Facial dysmorphism-Intellectual disability-rhombencephalosynapsis syndrome
TSC2	Orphanet:210159	Adult hepatocellular carcinoma
TSC2	Orphanet:269001	Isolated focal cortical dysplasia type IIa
TSC2	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC2	Orphanet:538	Lymphangioleiomyomatosis
TSC2	Orphanet:805	Tuberous sclerosis complex
TSC2	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MN1	HGNC:7180	ENSG00000169184	Q10571	Transcriptional activator MN1	civic_evidence
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MN1	Transcriptional activator MN1	Transcriptional activator which specifically regulates expression of TBX22 in the posterior region of the developing palate.
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MN1	Other/Unknown	no		MN1
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom

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
ganglionic eminence	1
skeletal muscle tissue of biceps brachii	1
vastus lateralis	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MN1	252	ubiquitous	marker	ganglionic eminence, vastus lateralis, skeletal muscle tissue of biceps brachii
TSC2	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATM	7,383
TSC2	4,135
MN1	902

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATM	Q13315	14
TSC2	P49815	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MN1	Q10571	42.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 67. Enrichment computed across 3 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
Macroautophagy	2	115.3×	0.005	TSC2, ATM
Inhibition of TSC complex formation by AKT (PKB)	1	1142.0×	0.012	TSC2
Sensing of DNA Double Strand Breaks	1	951.7×	0.012	ATM
TP53 Regulates Transcription of Caspase Activators and Caspases	1	475.8×	0.012	ATM
Pexophagy	1	475.8×	0.012	ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	475.8×	0.012	ATM
AKT phosphorylates targets in the cytosol	1	407.9×	0.012	TSC2
Diseases of DNA Double-Strand Break Repair	1	407.9×	0.012	ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	407.9×	0.012	ATM
Stabilization of p53	1	380.7×	0.012	ATM
p53-Dependent G1 DNA Damage Response	1	356.9×	0.012	ATM
p53-Dependent G1/S DNA damage checkpoint	1	356.9×	0.012	ATM
G1/S DNA Damage Checkpoints	1	335.9×	0.012	ATM
Resolution of D-Loop Structures	1	317.2×	0.012	ATM
Diseases of DNA repair	1	285.5×	0.012	ATM
TP53 Regulates Transcription of Cell Death Genes	1	271.9×	0.012	ATM
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	271.9×	0.012	ATM
Regulation of TP53 Activity through Methylation	1	271.9×	0.012	ATM
Regulation of TP53 Expression and Degradation	1	259.6×	0.012	ATM
DNA Double Strand Break Response	1	237.9×	0.012	ATM
Impaired BRCA2 binding to PALB2	1	228.4×	0.012	ATM
Constitutive Signaling by AKT1 E17K in Cancer	1	211.5×	0.012	TSC2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	211.5×	0.012	ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	211.5×	0.012	ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	211.5×	0.012	ATM
Cellular response to heat stress	1	196.9×	0.012	ATM
Energy dependent regulation of mTOR by LKB1-AMPK	1	196.9×	0.012	TSC2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	196.9×	0.012	ATM
Homologous DNA Pairing and Strand Exchange	1	190.3×	0.012	ATM
Homology Directed Repair	1	154.3×	0.013	ATM

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
negative regulation of TORC1 signaling	2	216.1×	0.003	TSC2, ATM
establishment of RNA localization to telomere	1	2808.7×	0.006	ATM
establishment of protein-containing complex localization to telomere	1	2808.7×	0.006	ATM
positive regulation of telomerase catalytic core complex assembly	1	2808.7×	0.006	ATM
pre-B cell allelic exclusion	1	1872.4×	0.006	ATM
cellular response to nitrosative stress	1	1872.4×	0.006	ATM
heart development	2	52.5×	0.006	TSC2, ATM
regulation of cell cycle	2	49.7×	0.006	TSC2, ATM
peptidyl-serine autophosphorylation	1	1123.5×	0.007	ATM
negative regulation of telomere capping	1	1123.5×	0.007	ATM
intramembranous ossification	1	936.2×	0.007	MN1
regulation of telomere maintenance via telomerase	1	936.2×	0.007	ATM
positive regulation of vitamin D receptor signaling pathway	1	936.2×	0.007	MN1
positive regulation of telomere maintenance via telomere lengthening	1	936.2×	0.007	ATM
lipoprotein catabolic process	1	802.5×	0.007	ATM
V(D)J recombination	1	702.2×	0.007	ATM
meiotic telomere clustering	1	624.1×	0.007	ATM
female meiotic nuclear division	1	561.7×	0.007	ATM
regulation of insulin receptor signaling pathway	1	561.7×	0.007	TSC2
histone mRNA catabolic process	1	561.7×	0.007	ATM
cellular response to X-ray	1	561.7×	0.007	ATM
DNA double-strand break processing	1	510.7×	0.007	ATM
negative regulation of osteoblast proliferation	1	510.7×	0.007	MN1
negative regulation of mitophagy	1	510.7×	0.007	TSC2
regulation of cell cycle G1/S phase transition	1	510.7×	0.007	MN1
anoikis	1	432.1×	0.008	TSC2
regulation of autophagosome assembly	1	374.5×	0.009	ATM
pexophagy	1	351.1×	0.009	ATM
regulation of cellular response to heat	1	351.1×	0.009	ATM
positive regulation of DNA damage response, signal transduction by p53 class mediator	1	330.4×	0.009	ATM

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATM	35	4
MN1	0	0
TSC2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ATM	240	Binding:233, Functional:5, ADMET:2
TSC2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240

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).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATM
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	MN1, TSC2

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)
MN1	0	—
TSC2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.