Complex cortical dysplasia with other brain malformations 1
disease diseaseOn this page
Also known as CDCBM1complex cortical dysplasia with other brain malformations caused by mutation in TUBB3complex cortical dysplasia with other brain malformations type 1cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutationcortical dysplasia, complex, with other brain malformations 1cortical dysplasia, Complex, with Other brain malformations type 1TUBB3 complex cortical dysplasia with other brain malformations
Summary
Complex cortical dysplasia with other brain malformations 1 (MONDO:0013541) is a disease caused by TUBB3 (GenCC Strong), with 4 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: TUBB3 (GenCC Strong)
- Cohort genes: 4
- ClinVar variants: 58
- Phenotypes (HPO): 79
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 12 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Signs & symptoms
Clinical features (HPO)
79 HPO clinical features (Orphanet curated; top 50 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0001250 | Seizure | Obligate (100%) |
| HP:0001263 | Global developmental delay | Very frequent (80-99%) |
| HP:0000486 | Strabismus | Frequent (30-79%) |
| HP:0000496 | Abnormality of eye movement | Frequent (30-79%) |
| HP:0000565 | Esotropia | Frequent (30-79%) |
| HP:0000639 | Nystagmus | Frequent (30-79%) |
| HP:0001249 | Intellectual disability | Frequent (30-79%) |
| HP:0001257 | Spasticity | Frequent (30-79%) |
| HP:0001321 | Cerebellar hypoplasia | Frequent (30-79%) |
| HP:0001338 | Partial agenesis of the corpus callosum | Frequent (30-79%) |
| HP:0001339 | Lissencephaly | Frequent (30-79%) |
| HP:0001488 | Bilateral ptosis | Frequent (30-79%) |
| HP:0002079 | Hypoplasia of the corpus callosum | Frequent (30-79%) |
| HP:0002126 | Polymicrogyria | Frequent (30-79%) |
| HP:0002194 | Delayed gross motor development | Frequent (30-79%) |
| HP:0002334 | Abnormality of the cerebellar vermis | Frequent (30-79%) |
| HP:0002365 | Hypoplasia of the brainstem | Frequent (30-79%) |
| HP:0002465 | Poor speech | Frequent (30-79%) |
| HP:0002474 | Expressive language delay | Frequent (30-79%) |
| HP:0002497 | Spastic ataxia | Frequent (30-79%) |
| HP:0002540 | Inability to walk | Frequent (30-79%) |
| HP:0007260 | Type II lissencephaly | Frequent (30-79%) |
| HP:0008872 | Feeding difficulties in infancy | Frequent (30-79%) |
| HP:0008897 | Postnatal growth retardation | Frequent (30-79%) |
| HP:0008936 | Axial hypotonia | Frequent (30-79%) |
| HP:0009879 | Simplified gyral pattern | Frequent (30-79%) |
| HP:0010862 | Delayed fine motor development | Frequent (30-79%) |
| HP:0011344 | Severe global developmental delay | Frequent (30-79%) |
| HP:0025336 | Delayed ability to sit | Frequent (30-79%) |
| HP:0000218 | High palate | Occasional (5-29%) |
| HP:0000256 | Macrocephaly | Occasional (5-29%) |
| HP:0000286 | Epicanthus | Occasional (5-29%) |
| HP:0000347 | Micrognathia | Occasional (5-29%) |
| HP:0000369 | Low-set ears | Occasional (5-29%) |
| HP:0000407 | Sensorineural hearing impairment | Occasional (5-29%) |
| HP:0000473 | Torticollis | Occasional (5-29%) |
| HP:0000494 | Downslanted palpebral fissures | Occasional (5-29%) |
| HP:0000570 | Abnormal saccadic eye movements | Occasional (5-29%) |
| HP:0000572 | Visual loss | Occasional (5-29%) |
| HP:0000609 | Optic nerve hypoplasia | Occasional (5-29%) |
| HP:0000657 | Oculomotor apraxia | Occasional (5-29%) |
| HP:0000712 | Emotional lability | Occasional (5-29%) |
| HP:0000733 | Abnormal repetitive mannerisms | Occasional (5-29%) |
| HP:0000736 | Short attention span | Occasional (5-29%) |
| HP:0001260 | Dysarthria | Occasional (5-29%) |
| HP:0001264 | Spastic diplegia | Occasional (5-29%) |
| HP:0001320 | Cerebellar vermis hypoplasia | Occasional (5-29%) |
| HP:0001332 | Dystonia | Occasional (5-29%) |
| HP:0001357 | Plagiocephaly | Occasional (5-29%) |
| HP:0001382 | Joint hypermobility | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | complex cortical dysplasia with other brain malformations 1 |
| Mondo ID | MONDO:0013541 |
| OMIM | 614039 |
| Orphanet | 300570 |
| DOID | DOID:0090137 |
| UMLS | C3808397 |
| MedGen | 814727 |
| GARD | 0013032 |
| Is cancer (heuristic) | no |
Also known as: CDCBM1 · complex cortical dysplasia with other brain malformations caused by mutation in TUBB3 · complex cortical dysplasia with other brain malformations type 1 · cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation · cortical dysplasia, complex, with other brain malformations 1 · cortical dysplasia, Complex, with Other brain malformations type 1 · TUBB3 complex cortical dysplasia with other brain malformations
Data availability: 58 ClinVar variants · 5 GenCC gene-disease records.
Disease family
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 › complex cortical dysplasia with other brain malformations 1
Related subtypes (11): complex cortical dysplasia with other brain malformations 7, polymicrogyria with optic nerve hypoplasia, 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
ClinVar germline variants
58 retrieved; paginated sample, class counts are floors:
17 uncertain significance, 10 conflicting classifications of pathogenicity, 9 pathogenic/likely pathogenic, 9 pathogenic, 8 likely pathogenic, 4 not provided, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2579671 | NC_000016.10:g.89944064G>A | Pathogenic | criteria provided, single submitter | |
| 160191 | NM_006086.4(TUBB3):c.292G>A (p.Gly98Ser) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 219255 | NM_006086.4(TUBB3):c.211G>A (p.Gly71Arg) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 219257 | NM_006086.4(TUBB3):c.1138C>T (p.Arg380Cys) | TUBB3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 236243 | NM_006086.4(TUBB3):c.1162A>G (p.Met388Val) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 265335 | NM_006086.4(TUBB3):c.533C>T (p.Thr178Met) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 265354 | NM_006086.4(TUBB3):c.1172G>T (p.Arg391Leu) | TUBB3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 280212 | NM_006086.4(TUBB3):c.689C>T (p.Ser230Leu) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 30272 | NM_006086.4(TUBB3):c.967A>G (p.Met323Val) | TUBB3 | Pathogenic | criteria provided, single submitter |
| 30274 | NM_006086.4(TUBB3):c.613G>A (p.Glu205Lys) | TUBB3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 30275 | NM_006086.4(TUBB3):c.905C>T (p.Ala302Val) | TUBB3 | Pathogenic | no assertion criteria provided |
| 372654 | NM_006086.4(TUBB3):c.763G>A (p.Val255Ile) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 384329 | NM_006086.4(TUBB3):c.862G>A (p.Glu288Lys) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 430312 | NM_006086.4(TUBB3):c.424G>A (p.Gly142Ser) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 520851 | NM_006086.4(TUBB3):c.523G>C (p.Val175Leu) | TUBB3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 6966 | NM_006086.4(TUBB3):c.1249G>A (p.Asp417Asn) | TUBB3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 6967 | NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys) | TUBB3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 975630 | NM_006086.4(TUBB3):c.577G>A (p.Val193Met) | TUBB3 | Pathogenic | no assertion criteria provided |
| 1320071 | NM_006086.4(TUBB3):c.178G>T (p.Val60Leu) | TUBB3 | Likely pathogenic | criteria provided, single submitter |
| 1320230 | NM_006086.4(TUBB3):c.1139G>C (p.Arg380Pro) | TUBB3 | Likely pathogenic | criteria provided, single submitter |
| 1679223 | NM_006086.4(TUBB3):c.929A>G (p.Tyr310Cys) | TUBB3 | Likely pathogenic | criteria provided, single submitter |
| 1708291 | NM_006086.4(TUBB3):c.817C>G (p.Leu273Val) | TUBB3 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1710200 | NM_006086.4(TUBB3):c.313C>A (p.His105Asn) | TUBB3 | Likely pathogenic | no assertion criteria provided |
| 2499586 | NM_006086.4(TUBB3):c.1138C>A (p.Arg380Ser) | TUBB3 | Likely pathogenic | criteria provided, single submitter |
| 4056411 | NM_006086.4(TUBB3):c.613G>C (p.Glu205Gln) | TUBB3 | Likely pathogenic | criteria provided, single submitter |
| 931842 | NM_006086.4(TUBB3):c.863A>C (p.Glu288Ala) | TUBB3 | Likely pathogenic | criteria provided, single submitter |
| 2108986 | NM_006086.4(TUBB3):c.5G>A (p.Arg2Lys) | LOC130059847 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1198880 | NM_006086.4(TUBB3):c.805G>A (p.Gly269Ser) | TUBB3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1303397 | NM_006086.4(TUBB3):c.935C>T (p.Thr312Met) | TUBB3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1326540 | NM_006086.4(TUBB3):c.925C>T (p.Arg309Cys) | TUBB3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 11 · Orphanet: 8 · 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 |
|---|---|---|---|---|
| TUBB3 | Strong | Autosomal dominant | complex cortical dysplasia with other brain malformations 1 | 11 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TUBB3 | Orphanet:300570 | Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation |
| TUBB3 | Orphanet:45358 | Congenital fibrosis of extraocular muscles |
| TUBB3 | Orphanet:467166 | Tubulinopathy-associated dysgyria |
| APC2 | Orphanet:821 | Sotos syndrome |
| 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
4 cohort genes, 4 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TUBB3 | HGNC:20772 | ENSG00000258947 | Q13509 | Tubulin beta-3 chain | gencc,clinvar |
| SLC25A23 | HGNC:19375 | ENSG00000125648 | Q9BV35 | Mitochondrial adenyl nucleotide antiporter SLC25A23 | clinvar |
| APC2 | HGNC:24036 | ENSG00000115266 | O95996 | Adenomatous polyposis coli protein 2 | clinvar |
| TUBB2B | HGNC:30829 | ENSG00000137285 | Q9BVA1 | Tubulin beta-2B chain | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TUBB3 | Tubulin beta-3 chain | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers. |
| SLC25A23 | Mitochondrial adenyl nucleotide antiporter SLC25A23 | Electroneutral antiporter that mediates the transport of adenine nucleotides through the inner mitochondrial membrane. |
| APC2 | Adenomatous polyposis coli protein 2 | Stabilizes microtubules and may regulate actin fiber dynamics through the activation of Rho family GTPases. |
| 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: 4 · 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 | 4 | 1.8× | 0.097 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TUBB3 | Other/Unknown | no | Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase | |
| SLC25A23 | Other/Unknown | no | EF_hand_dom, MCP, EF-hand-dom_pair | |
| APC2 | Other/Unknown | no | Armadillo, APC_rpt, SAMP | |
| TUBB2B | Other/Unknown | no | Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase |
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) | 4 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cortical plate | 3 |
| ganglionic eminence | 2 |
| embryo | 1 |
| buccal mucosa cell | 1 |
| caudate nucleus | 1 |
| nucleus accumbens | 1 |
| cerebellar vermis | 1 |
| paraflocculus | 1 |
| ventricular zone | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TUBB3 | 144 | ubiquitous | marker | cortical plate, ganglionic eminence, embryo |
| SLC25A23 | 271 | ubiquitous | marker | nucleus accumbens, caudate nucleus, buccal mucosa cell |
| APC2 | 199 | broad | yes | paraflocculus, cortical plate, cerebellar vermis |
| TUBB2B | 265 | ubiquitous | marker | cortical plate, ganglionic eminence, ventricular zone |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TUBB3 | 6,797 |
| TUBB2B | 4,736 |
| SLC25A23 | 1,383 |
| APC2 | 963 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| TUBB2B | TUBB3 | biogrid_interaction |
Structural data
PDB: 2 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TUBB3 | Q13509 | 28 |
| TUBB2B | Q9BVA1 | 3 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SLC25A23 | Q9BV35 | 78.93 |
| APC2 | O95996 | 48.87 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 86. Enrichment computed across 4 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 |
|---|---|---|---|---|
| Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 2 | 543.8× | 6e-05 | TUBB3, TUBB2B |
| Transport of connexons to the plasma membrane | 2 | 543.8× | 6e-05 | TUBB3, TUBB2B |
| Gap junction trafficking and regulation | 2 | 475.8× | 6e-05 | TUBB3, TUBB2B |
| Gap junction trafficking | 2 | 475.8× | 6e-05 | TUBB3, TUBB2B |
| Post-chaperonin tubulin folding pathway | 2 | 475.8× | 6e-05 | TUBB3, TUBB2B |
| Formation of tubulin folding intermediates by CCT/TriC | 2 | 423.0× | 6e-05 | TUBB3, TUBB2B |
| Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 2 | 407.9× | 6e-05 | TUBB3, TUBB2B |
| Prefoldin mediated transfer of substrate to CCT/TriC | 2 | 393.8× | 6e-05 | TUBB3, TUBB2B |
| Activation of AMPK downstream of NMDARs | 2 | 380.7× | 6e-05 | TUBB3, TUBB2B |
| RHO GTPases activate IQGAPs | 2 | 346.1× | 6e-05 | TUBB3, TUBB2B |
| Sealing of the nuclear envelope (NE) by ESCRT-III | 2 | 346.1× | 6e-05 | TUBB3, TUBB2B |
| HCMV Infection | 2 | 326.3× | 7e-05 | TUBB3, TUBB2B |
| Chaperonin-mediated protein folding | 2 | 300.5× | 7e-05 | TUBB3, TUBB2B |
| Gap junction assembly | 2 | 292.8× | 7e-05 | TUBB3, TUBB2B |
| Nuclear Envelope (NE) Reassembly | 2 | 292.8× | 7e-05 | TUBB3, TUBB2B |
| Selective autophagy | 2 | 278.5× | 7e-05 | TUBB3, TUBB2B |
| Protein folding | 2 | 259.6× | 7e-05 | TUBB3, TUBB2B |
| Assembly and cell surface presentation of NMDA receptors | 2 | 253.8× | 7e-05 | TUBB3, TUBB2B |
| Cargo trafficking to the periciliary membrane | 2 | 248.3× | 7e-05 | TUBB3, TUBB2B |
| Aggrephagy | 2 | 248.3× | 7e-05 | TUBB3, TUBB2B |
| Carboxyterminal post-translational modifications of tubulin | 2 | 237.9× | 7e-05 | TUBB3, TUBB2B |
| Recycling pathway of L1 | 2 | 223.9× | 8e-05 | TUBB3, TUBB2B |
| COPI-independent Golgi-to-ER retrograde traffic | 2 | 207.6× | 8e-05 | TUBB3, TUBB2B |
| Post NMDA receptor activation events | 2 | 203.9× | 8e-05 | TUBB3, TUBB2B |
| Intraflagellar transport | 2 | 200.3× | 8e-05 | TUBB3, TUBB2B |
| Antimicrobial mechanism of IFN-stimulated genes | 2 | 196.9× | 8e-05 | TUBB3, TUBB2B |
| HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand | 2 | 193.6× | 8e-05 | TUBB3, TUBB2B |
| Activation of NMDA receptors and postsynaptic events | 2 | 184.2× | 9e-05 | TUBB3, TUBB2B |
| Signaling by Hedgehog | 2 | 184.2× | 9e-05 | TUBB3, TUBB2B |
| Hedgehog ‘off’ state | 2 | 178.4× | 9e-05 | TUBB3, 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| microtubule cytoskeleton organization | 3 | 90.9× | 7e-05 | TUBB3, APC2, TUBB2B |
| obsolete regulation of sequestering of calcium ion | 1 | 2106.5× | 0.004 | SLC25A23 |
| positive regulation of axon guidance | 1 | 2106.5× | 0.004 | TUBB2B |
| mitotic cell cycle | 2 | 66.9× | 0.004 | TUBB3, TUBB2B |
| adenine nucleotide transport | 1 | 1053.2× | 0.005 | SLC25A23 |
| regulation of cellular hyperosmotic salinity response | 1 | 842.6× | 0.005 | SLC25A23 |
| dorsal root ganglion development | 1 | 842.6× | 0.005 | TUBB3 |
| ADP transport | 1 | 526.6× | 0.007 | SLC25A23 |
| mitochondrial ATP transmembrane transport | 1 | 468.1× | 0.007 | SLC25A23 |
| positive regulation of mitochondrial calcium ion concentration | 1 | 421.3× | 0.007 | SLC25A23 |
| ATP transport | 1 | 351.1× | 0.008 | SLC25A23 |
| regulation of oxidative phosphorylation | 1 | 300.9× | 0.008 | SLC25A23 |
| calcium import into the mitochondrion | 1 | 300.9× | 0.008 | SLC25A23 |
| renal system process | 1 | 280.9× | 0.008 | SLC25A23 |
| mitochondrial calcium ion transmembrane transport | 1 | 247.8× | 0.008 | SLC25A23 |
| microtubule-based process | 1 | 247.8× | 0.008 | TUBB2B |
| embryonic brain development | 1 | 200.6× | 0.009 | TUBB2B |
| activation of GTPase activity | 1 | 183.2× | 0.009 | APC2 |
| cell fate specification | 1 | 131.7× | 0.012 | APC2 |
| negative regulation of microtubule depolymerization | 1 | 123.9× | 0.012 | APC2 |
| pattern specification process | 1 | 117.0× | 0.013 | APC2 |
| cerebral cortex development | 1 | 51.4× | 0.027 | TUBB2B |
| cellular response to calcium ion | 1 | 50.1× | 0.027 | SLC25A23 |
| modulation of chemical synaptic transmission | 1 | 45.8× | 0.028 | TUBB2B |
| neuron migration | 1 | 33.4× | 0.037 | TUBB2B |
| negative regulation of canonical Wnt signaling pathway | 1 | 29.5× | 0.040 | APC2 |
| Wnt signaling pathway | 1 | 24.9× | 0.045 | APC2 |
| axon guidance | 1 | 22.6× | 0.048 | TUBB3 |
| cell migration | 1 | 15.4× | 0.068 | APC2 |
| proteasome-mediated ubiquitin-dependent protein catabolic process | 1 | 13.0× | 0.077 | APC2 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2
Druggability breadth: 2 of 4 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 |
|---|---|
| TUBB3 | COLCHICINE |
| TUBB2B | COLCHICINE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TUBB3 | 21 | 4 |
| TUBB2B | 21 | 4 |
| SLC25A23 | 0 | 0 |
| APC2 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| COLCHICINE | 4 | TUBB2B, TUBB3 |
| VINBLASTINE | 4 | TUBB2B, TUBB3 |
| LEVOFLOXACIN ANHYDROUS | 4 | TUBB2B, TUBB3 |
| DOCETAXEL | 4 | TUBB2B, TUBB3 |
| NOSCAPINE | 4 | TUBB2B, TUBB3 |
| VINBLASTINE SULFATE | 4 | TUBB2B, TUBB3 |
| PACLITAXEL | 4 | TUBB2B, TUBB3 |
| LEVOFLOXACIN | 4 | TUBB2B, TUBB3 |
| VINORELBINE | 4 | TUBB2B, TUBB3 |
| TIRBANIBULIN | 4 | TUBB2B, TUBB3 |
| PODOFILOX | 4 | TUBB2B, TUBB3 |
| VINCRISTINE | 4 | TUBB2B, TUBB3 |
| DOCETAXEL ANHYDROUS | 4 | TUBB2B, TUBB3 |
| PATUPILONE | 3 | TUBB2B, TUBB3 |
| ABT-751 | 2 | TUBB2B, TUBB3 |
| MAYTANSINE | 2 | TUBB2B, TUBB3 |
| DOLASTATIN-10 | 2 | TUBB2B, TUBB3 |
| INDIBULIN | 2 | TUBB2B, TUBB3 |
| PARBENDAZOLE | 2 | TUBB2B, TUBB3 |
| NOCODAZOLE | 2 | TUBB2B, TUBB3 |
| COMBRETASTATIN | 1 | TUBB2B, TUBB3 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TUBB3 | 1,781 | Binding:1741, Functional:34, ADMET:6 |
| 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 |
|---|---|
| TUBB3 | 1,781 |
| TUBB2B | 1,757 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 4; 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, TUBB3 |
| VINBLASTINE | 4 | TUBB2B, TUBB3 |
| LEVOFLOXACIN ANHYDROUS | 4 | TUBB2B, TUBB3 |
| DOCETAXEL | 4 | TUBB2B, TUBB3 |
| NOSCAPINE | 4 | TUBB2B, TUBB3 |
| VINBLASTINE SULFATE | 4 | TUBB2B, TUBB3 |
| PACLITAXEL | 4 | TUBB2B, TUBB3 |
| LEVOFLOXACIN | 4 | TUBB2B, TUBB3 |
| VINORELBINE | 4 | TUBB2B, TUBB3 |
| TIRBANIBULIN | 4 | TUBB2B, TUBB3 |
| PODOFILOX | 4 | TUBB2B, TUBB3 |
| VINCRISTINE | 4 | TUBB2B, TUBB3 |
| DOCETAXEL ANHYDROUS | 4 | TUBB2B, TUBB3 |
| PATUPILONE | 3 | TUBB2B, TUBB3 |
| ABT-751 | 2 | TUBB2B, TUBB3 |
| MAYTANSINE | 2 | TUBB2B, TUBB3 |
| DOLASTATIN-10 | 2 | TUBB2B, TUBB3 |
| INDIBULIN | 2 | TUBB2B, TUBB3 |
| PARBENDAZOLE | 2 | TUBB2B, TUBB3 |
| NOCODAZOLE | 2 | TUBB2B, TUBB3 |
| COMBRETASTATIN | 1 | TUBB2B, TUBB3 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | TUBB3, 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 | 2 | SLC25A23, APC2 |
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) |
|---|---|---|
| SLC25A23 | 0 | — |
| APC2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.