Complex cortical dysplasia with other brain malformations

Summary

Complex cortical dysplasia with other brain malformations (MONDO:0000904) is a disease (an umbrella term covering 12 Mondo subtypes) caused by TUBB2B (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TUBB2B (GenCC Definitive)
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	complex cortical dysplasia with other brain malformations
Mondo ID	MONDO:0000904
OMIM	614039
DOID	DOID:0090131
Is cancer (heuristic)	no

Also known as: complex cortical dysplasia with other brain malformations · cortical dysplasia, complex, with other brain malformations

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 12 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › complex cortical dysplasia with other brain malformations

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (12): complex cortical dysplasia with other brain malformations 7, polymicrogyria with optic nerve hypoplasia, complex cortical dysplasia with other brain malformations 1, complex cortical dysplasia with other brain malformations 2, complex cortical dysplasia with other brain malformations 3, complex cortical dysplasia with other brain malformations 4, complex cortical dysplasia with other brain malformations 5, complex cortical dysplasia with other brain malformations 6, cortical dysplasia, complex, with other brain malformations 9, cortical dysplasia, complex, with other brain malformations 10, cortical dysplasia, complex, with other brain malformations 11, cortical dysplasia, complex, with other brain malformations 12

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: 9 · Orphanet: 4 · 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
TUBB2B	Definitive	Autosomal dominant	complex cortical dysplasia with other brain malformations	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBB2B	Orphanet:1766	Dysequilibrium syndrome
TUBB2B	Orphanet:300573	Polymicrogyria due to TUBB2B mutation
TUBB2B	Orphanet:45358	Congenital fibrosis of extraocular muscles
TUBB2B	Orphanet:467166	Tubulinopathy-associated dysgyria

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TUBB2B	HGNC:30829	ENSG00000137285	Q9BVA1	Tubulin beta-2B chain	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBB2B	Tubulin beta-2B chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUBB2B	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBB2B	265	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB2B	4,736

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUBB2B	Q9BVA1	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 86. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	543.8×	0.016	TUBB2B
Transport of connexons to the plasma membrane	1	543.8×	0.016	TUBB2B
Gap junction trafficking and regulation	1	475.8×	0.016	TUBB2B
Gap junction trafficking	1	475.8×	0.016	TUBB2B
Post-chaperonin tubulin folding pathway	1	475.8×	0.016	TUBB2B
Formation of tubulin folding intermediates by CCT/TriC	1	423.0×	0.016	TUBB2B
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	407.9×	0.016	TUBB2B
Prefoldin mediated transfer of substrate to CCT/TriC	1	393.8×	0.016	TUBB2B
Activation of AMPK downstream of NMDARs	1	380.7×	0.016	TUBB2B
RHO GTPases activate IQGAPs	1	346.1×	0.016	TUBB2B
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.016	TUBB2B
HCMV Infection	1	326.3×	0.016	TUBB2B
Chaperonin-mediated protein folding	1	300.5×	0.016	TUBB2B
Gap junction assembly	1	292.8×	0.016	TUBB2B
Nuclear Envelope (NE) Reassembly	1	292.8×	0.016	TUBB2B
Selective autophagy	1	278.5×	0.016	TUBB2B
Protein folding	1	259.6×	0.016	TUBB2B
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.016	TUBB2B
Cargo trafficking to the periciliary membrane	1	248.3×	0.016	TUBB2B
Aggrephagy	1	248.3×	0.016	TUBB2B
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.016	TUBB2B
Recycling pathway of L1	1	223.9×	0.016	TUBB2B
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.016	TUBB2B
Post NMDA receptor activation events	1	203.9×	0.016	TUBB2B
Intraflagellar transport	1	200.3×	0.016	TUBB2B
Antimicrobial mechanism of IFN-stimulated genes	1	196.9×	0.016	TUBB2B
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.016	TUBB2B
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.016	TUBB2B
Signaling by Hedgehog	1	184.2×	0.016	TUBB2B
Hedgehog ‘off’ state	1	178.4×	0.016	TUBB2B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 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 axon guidance	1	8426.0×	9e-04	TUBB2B
microtubule-based process	1	991.3×	0.003	TUBB2B
embryonic brain development	1	802.5×	0.003	TUBB2B
cerebral cortex development	1	205.5×	0.008	TUBB2B
modulation of chemical synaptic transmission	1	183.2×	0.008	TUBB2B
mitotic cell cycle	1	133.8×	0.008	TUBB2B
neuron migration	1	133.8×	0.008	TUBB2B
microtubule cytoskeleton organization	1	121.2×	0.008	TUBB2B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
TUBB2B	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB2B	21	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB2B
VINBLASTINE	4	TUBB2B
LEVOFLOXACIN ANHYDROUS	4	TUBB2B
DOCETAXEL	4	TUBB2B
NOSCAPINE	4	TUBB2B
VINBLASTINE SULFATE	4	TUBB2B
PACLITAXEL	4	TUBB2B
LEVOFLOXACIN	4	TUBB2B
VINORELBINE	4	TUBB2B
TIRBANIBULIN	4	TUBB2B
PODOFILOX	4	TUBB2B
VINCRISTINE	4	TUBB2B
DOCETAXEL ANHYDROUS	4	TUBB2B
PATUPILONE	3	TUBB2B
ABT-751	2	TUBB2B
MAYTANSINE	2	TUBB2B
DOLASTATIN-10	2	TUBB2B
INDIBULIN	2	TUBB2B
PARBENDAZOLE	2	TUBB2B
NOCODAZOLE	2	TUBB2B
COMBRETASTATIN	1	TUBB2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBB2B	1,757	Binding:1717, 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
TUBB2B	1,757

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	TUBB2B
VINBLASTINE	4	TUBB2B
LEVOFLOXACIN ANHYDROUS	4	TUBB2B
DOCETAXEL	4	TUBB2B
NOSCAPINE	4	TUBB2B
VINBLASTINE SULFATE	4	TUBB2B
PACLITAXEL	4	TUBB2B
LEVOFLOXACIN	4	TUBB2B
VINORELBINE	4	TUBB2B
TIRBANIBULIN	4	TUBB2B
PODOFILOX	4	TUBB2B
VINCRISTINE	4	TUBB2B
DOCETAXEL ANHYDROUS	4	TUBB2B
PATUPILONE	3	TUBB2B
ABT-751	2	TUBB2B
MAYTANSINE	2	TUBB2B
DOLASTATIN-10	2	TUBB2B
INDIBULIN	2	TUBB2B
PARBENDAZOLE	2	TUBB2B
NOCODAZOLE	2	TUBB2B
COMBRETASTATIN	1	TUBB2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBB2B
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.