Classic medulloblastoma

Summary

Classic medulloblastoma (MONDO:0016712) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	classic medulloblastoma
Mondo ID	MONDO:0016712
Orphanet	251867
ICD-11	1548011794
NCIT	C54039
SNOMED CT	699704002
UMLS	C1707400
MedGen	353541
GARD	0017216
Is cancer (heuristic)	no

Also known as: classic medulloblastoma

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebellar disorder › cerebellar neoplasm › medulloblastoma › classic medulloblastoma

Related subtypes (13): brain stem medulloblastoma, large cell medulloblastoma, cerebellar vermis medulloblastoma, adult medulloblastoma, melanotic medulloblastoma, childhood medulloblastoma, medullomyoblastoma with myogenic differentiation, anaplastic/large cell medulloblastoma, medulloblastoma with extensive nodularity, desmoplastic/nodular medulloblastoma, medulloblastoma WNT activated, medulloblastoma SHH activated, medulloblastoma non-WNT/non-SHH

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 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802532	NM_020987.5(ANK3):c.7068dup (p.Glu2357fs)	ANK3	Pathogenic	criteria provided, single submitter
1802531	NM_006087.4(TUBB4A):c.571C>T (p.Gln191Ter)	TUBB4A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBB4A	Orphanet:139441	Hypomyelination with atrophy of basal ganglia and cerebellum
TUBB4A	Orphanet:98805	Primary dystonia, DYT4 type
ANK3	Orphanet:356996	ANK3-related intellectual disability-sleep disturbance syndrome

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
TUBB4A	HGNC:20774	ENSG00000104833	P04350	Tubulin beta-4A chain	clinvar
ANK3	HGNC:494	ENSG00000151150	Q12955	Ankyrin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBB4A	Tubulin beta-4A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
ANK3	Ankyrin-3	Membrane-cytoskeleton linker.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUBB4A	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
ANK3	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
Brodmann (1909) area 23	1
dorsal motor nucleus of vagus nerve	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBB4A	201	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
ANK3	298	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK3	6,145
TUBB4A	5,138

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANK3	Q12955	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBB4A	P04350	92.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 95. 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
ER to Golgi Anterograde Transport	2	132.8×	0.002	TUBB4A, ANK3
L1CAM interactions	2	120.2×	0.002	TUBB4A, ANK3
COPI-mediated anterograde transport	2	109.8×	0.002	TUBB4A, ANK3
Transport to the Golgi and subsequent modification	2	102.9×	0.002	TUBB4A, ANK3
Asparagine N-linked glycosylation	2	60.1×	0.005	TUBB4A, ANK3
Axon guidance	2	45.1×	0.007	TUBB4A, ANK3
Nervous system development	2	42.9×	0.007	TUBB4A, ANK3
Membrane Trafficking	2	37.1×	0.009	TUBB4A, ANK3
Vesicle-mediated transport	2	34.8×	0.009	TUBB4A, ANK3
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	271.9×	0.022	TUBB4A
Transport of connexons to the plasma membrane	1	271.9×	0.022	TUBB4A
Gap junction trafficking and regulation	1	237.9×	0.022	TUBB4A
Gap junction trafficking	1	237.9×	0.022	TUBB4A
Post-chaperonin tubulin folding pathway	1	237.9×	0.022	TUBB4A
Formation of tubulin folding intermediates by CCT/TriC	1	211.5×	0.022	TUBB4A
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	203.9×	0.022	TUBB4A
Prefoldin mediated transfer of substrate to CCT/TriC	1	196.9×	0.022	TUBB4A
Activation of AMPK downstream of NMDARs	1	190.3×	0.022	TUBB4A
Interaction between L1 and Ankyrins	1	184.2×	0.022	ANK3
RHO GTPases activate IQGAPs	1	173.0×	0.022	TUBB4A
Sealing of the nuclear envelope (NE) by ESCRT-III	1	173.0×	0.022	TUBB4A
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.022	ANK3
HCMV Infection	1	163.1×	0.022	TUBB4A
Chaperonin-mediated protein folding	1	150.3×	0.022	TUBB4A
Gap junction assembly	1	146.4×	0.022	TUBB4A
Nuclear Envelope (NE) Reassembly	1	146.4×	0.022	TUBB4A
Selective autophagy	1	139.3×	0.022	TUBB4A
Protein folding	1	129.8×	0.022	TUBB4A
Centrosome maturation	1	126.9×	0.022	TUBB4A
Assembly and cell surface presentation of NMDA receptors	1	126.9×	0.022	TUBB4A

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 cell communication by electrical coupling	1	4213.0×	0.002	ANK3
maintenance of protein location in plasma membrane	1	4213.0×	0.002	ANK3
positive regulation of membrane depolarization during cardiac muscle cell action potential	1	4213.0×	0.002	ANK3
membrane assembly	1	2106.5×	0.002	ANK3
protein localization to axon	1	1685.2×	0.002	ANK3
positive regulation of membrane potential	1	1404.3×	0.002	ANK3
negative regulation of delayed rectifier potassium channel activity	1	1404.3×	0.002	ANK3
positive regulation of homotypic cell-cell adhesion	1	1203.7×	0.002	ANK3
cellular response to magnesium ion	1	1203.7×	0.002	ANK3
magnesium ion homeostasis	1	936.2×	0.003	ANK3
regulation of potassium ion transport	1	936.2×	0.003	ANK3
negative regulation of microtubule polymerization	1	648.1×	0.003	TUBB4A
plasma membrane organization	1	443.5×	0.004	ANK3
positive regulation of sodium ion transport	1	421.3×	0.004	ANK3
positive regulation of protein targeting to membrane	1	280.9×	0.006	ANK3
neuromuscular junction development	1	263.3×	0.006	ANK3
Golgi to plasma membrane protein transport	1	263.3×	0.006	ANK3
neuronal action potential	1	240.7×	0.006	ANK3
establishment of protein localization	1	216.1×	0.006	ANK3
mitotic cytokinesis	1	129.6×	0.010	ANK3
axonogenesis	1	80.2×	0.015	ANK3
mitotic cell cycle	1	66.9×	0.018	TUBB4A
microtubule cytoskeleton organization	1	60.6×	0.019	TUBB4A
protein localization to plasma membrane	1	54.4×	0.020	ANK3
positive regulation of gene expression	1	19.4×	0.053	ANK3
signal transduction	1	8.0×	0.121	ANK3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
TUBB4A	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB4A	21	4
ANK3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB4A
VINBLASTINE	4	TUBB4A
LEVOFLOXACIN ANHYDROUS	4	TUBB4A
DOCETAXEL	4	TUBB4A
NOSCAPINE	4	TUBB4A
VINBLASTINE SULFATE	4	TUBB4A
PACLITAXEL	4	TUBB4A
LEVOFLOXACIN	4	TUBB4A
VINORELBINE	4	TUBB4A
TIRBANIBULIN	4	TUBB4A
PODOFILOX	4	TUBB4A
VINCRISTINE	4	TUBB4A
DOCETAXEL ANHYDROUS	4	TUBB4A
PATUPILONE	3	TUBB4A
ABT-751	2	TUBB4A
MAYTANSINE	2	TUBB4A
DOLASTATIN-10	2	TUBB4A
INDIBULIN	2	TUBB4A
PARBENDAZOLE	2	TUBB4A
NOCODAZOLE	2	TUBB4A
COMBRETASTATIN	1	TUBB4A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBB4A	1,758	Binding:1718, Functional:34, ADMET:6

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBB4A	1,758

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

21 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)
COLCHICINE	4	TUBB4A
VINBLASTINE	4	TUBB4A
LEVOFLOXACIN ANHYDROUS	4	TUBB4A
DOCETAXEL	4	TUBB4A
NOSCAPINE	4	TUBB4A
VINBLASTINE SULFATE	4	TUBB4A
PACLITAXEL	4	TUBB4A
LEVOFLOXACIN	4	TUBB4A
VINORELBINE	4	TUBB4A
TIRBANIBULIN	4	TUBB4A
PODOFILOX	4	TUBB4A
VINCRISTINE	4	TUBB4A
DOCETAXEL ANHYDROUS	4	TUBB4A
PATUPILONE	3	TUBB4A
ABT-751	2	TUBB4A
MAYTANSINE	2	TUBB4A
DOLASTATIN-10	2	TUBB4A
INDIBULIN	2	TUBB4A
PARBENDAZOLE	2	TUBB4A
NOCODAZOLE	2	TUBB4A
COMBRETASTATIN	1	TUBB4A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBB4A
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	ANK3

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)
ANK3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.