Cortical dysplasia, complex, with other brain malformations 10
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Also known as CDCBM10
Summary
Cortical dysplasia, complex, with other brain malformations 10 (MONDO:0032866) is a disease caused by APC2 (GenCC Strong), with 2 cohort genes.
At a glance
- Causal gene: APC2 (GenCC Strong)
- Cohort genes: 2
- ClinVar variants: 29
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | cortical dysplasia, complex, with other brain malformations 10 |
| Mondo ID | MONDO:0032866 |
| OMIM | 618677 |
| DOID | DOID:0061143 |
| UMLS | C5231458 |
| MedGen | 1684859 |
| Is cancer (heuristic) | no |
Also known as: CDCBM10
Data availability: 29 ClinVar variants · 4 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 › cortical dysplasia, complex, with other brain malformations 10
Related subtypes (11): 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 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
29 retrieved; paginated sample, class counts are floors:
18 uncertain significance, 4 likely pathogenic, 4 pathogenic, 2 benign, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 694620 | NM_005883.3(APC2):c.1081C>T (p.Gln361Ter) | APC2 | Pathogenic | no assertion criteria provided |
| 694621 | NM_005883.3(APC2):c.6645del (p.Ala2217fs) | APC2 | Pathogenic | no assertion criteria provided |
| 694622 | NM_005883.3(APC2):c.737C>A (p.Ser246Ter) | APC2 | Pathogenic | no assertion criteria provided |
| 694623 | NM_005883.3(APC2):c.2840_2846del (p.Leu947fs) | APC2 | Pathogenic | no assertion criteria provided |
| 2444065 | NM_005883.3(APC2):c.3397C>T (p.Arg1133Ter) | APC2 | Likely pathogenic | criteria provided, single submitter |
| 2444253 | NM_005883.3(APC2):c.759dup (p.Glu254fs) | APC2 | Likely pathogenic | criteria provided, single submitter |
| 3377276 | NM_005883.3(APC2):c.2931del (p.Glu977fs) | APC2 | Likely pathogenic | criteria provided, single submitter |
| 4796569 | NM_005883.3(APC2):c.935dup (p.Cys313fs) | APC2 | Likely pathogenic | criteria provided, single submitter |
| 741140 | NM_005883.3(APC2):c.3656C>T (p.Ala1219Val) | APC2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1028956 | NM_005883.3(APC2):c.4616G>C (p.Arg1539Pro) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1184368 | NM_005883.3(APC2):c.3011T>G (p.Leu1004Arg) | APC2 | Uncertain significance | criteria provided, single submitter |
| 1683633 | NM_005883.3(APC2):c.2595C>A (p.His865Gln) | APC2 | Uncertain significance | criteria provided, single submitter |
| 1805267 | NM_005883.3(APC2):c.4531G>A (p.Gly1511Ser) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2152625 | NM_005883.3(APC2):c.1465G>A (p.Gly489Ser) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2251001 | NM_005883.3(APC2):c.1796G>A (p.Ser599Asn) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2388426 | NM_005883.3(APC2):c.4949G>A (p.Arg1650His) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2441668 | NM_005883.3(APC2):c.3241C>G (p.Arg1081Gly) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3377714 | NM_005883.3(APC2):c.5936T>C (p.Leu1979Pro) | APC2 | Uncertain significance | criteria provided, single submitter |
| 3377715 | NM_005883.3(APC2):c.141+6G>A | APC2 | Uncertain significance | criteria provided, single submitter |
| 3412885 | NM_005883.3(APC2):c.5872G>C (p.Gly1958Arg) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3583510 | NM_005883.3(APC2):c.2372C>T (p.Ala791Val) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3583511 | NM_005883.3(APC2):c.2518_2523dup (p.Ala841_Lys842insAlaAla) | APC2 | Uncertain significance | criteria provided, single submitter |
| 3583512 | NM_005883.3(APC2):c.5123G>T (p.Arg1708Leu) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3731351 | NM_005883.3(APC2):c.5765A>T (p.Lys1922Met) | APC2 | Uncertain significance | criteria provided, single submitter |
| 493243 | NM_005883.3(APC2):c.5108C>A (p.Ala1703Glu) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 591864 | NM_005883.3(APC2):c.322_323inv (p.Ser108Leu) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 978190 | NM_005883.3(APC2):c.3979C>T (p.Pro1327Ser) | APC2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1185403 | NM_005883.3(APC2):c.413+95T>C | APC2 | Benign | criteria provided, multiple submitters, no conflicts |
| 1185404 | NM_005883.3(APC2):c.4384A>C (p.Arg1462=) | APC2 | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 12 · Orphanet: 1 · 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 |
|---|---|---|---|---|
| APC2 | Strong | Autosomal recessive | cortical dysplasia, complex, with other brain malformations 10 | 6 |
| SLC25A23 | Strong | Autosomal recessive | cortical dysplasia, complex, with other brain malformations 10 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| APC2 | Orphanet:821 | Sotos 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 |
|---|---|---|---|---|---|
| SLC25A23 | HGNC:19375 | ENSG00000125648 | Q9BV35 | Mitochondrial adenyl nucleotide antiporter SLC25A23 | gencc,clinvar |
| APC2 | HGNC:24036 | ENSG00000115266 | O95996 | Adenomatous polyposis coli protein 2 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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. |
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) |
|---|---|---|---|---|
| SLC25A23 | Other/Unknown | no | EF_hand_dom, MCP, EF-hand-dom_pair | |
| APC2 | Other/Unknown | no | Armadillo, APC_rpt, SAMP |
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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| buccal mucosa cell | 1 |
| caudate nucleus | 1 |
| nucleus accumbens | 1 |
| cerebellar vermis | 1 |
| cortical plate | 1 |
| paraflocculus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SLC25A23 | 271 | ubiquitous | marker | nucleus accumbens, caudate nucleus, buccal mucosa cell |
| APC2 | 199 | broad | yes | paraflocculus, cortical plate, cerebellar vermis |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SLC25A23 | 1,383 |
| APC2 | 963 |
Structural data
PDB: 0 · AlphaFold-only: 2 · No structure: 0
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: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| obsolete regulation of sequestering of calcium ion | 1 | 4213.0× | 0.004 | SLC25A23 |
| adenine nucleotide transport | 1 | 2106.5× | 0.004 | SLC25A23 |
| regulation of cellular hyperosmotic salinity response | 1 | 1685.2× | 0.004 | SLC25A23 |
| ADP transport | 1 | 1053.2× | 0.004 | SLC25A23 |
| mitochondrial ATP transmembrane transport | 1 | 936.2× | 0.004 | SLC25A23 |
| positive regulation of mitochondrial calcium ion concentration | 1 | 842.6× | 0.004 | SLC25A23 |
| ATP transport | 1 | 702.2× | 0.004 | SLC25A23 |
| regulation of oxidative phosphorylation | 1 | 601.9× | 0.004 | SLC25A23 |
| calcium import into the mitochondrion | 1 | 601.9× | 0.004 | SLC25A23 |
| renal system process | 1 | 561.7× | 0.004 | SLC25A23 |
| mitochondrial calcium ion transmembrane transport | 1 | 495.6× | 0.004 | SLC25A23 |
| activation of GTPase activity | 1 | 366.4× | 0.005 | APC2 |
| cell fate specification | 1 | 263.3× | 0.006 | APC2 |
| negative regulation of microtubule depolymerization | 1 | 247.8× | 0.006 | APC2 |
| pattern specification process | 1 | 234.1× | 0.006 | APC2 |
| cellular response to calcium ion | 1 | 100.3× | 0.014 | SLC25A23 |
| microtubule cytoskeleton organization | 1 | 60.6× | 0.021 | APC2 |
| negative regulation of canonical Wnt signaling pathway | 1 | 58.9× | 0.021 | APC2 |
| Wnt signaling pathway | 1 | 49.9× | 0.023 | APC2 |
| cell migration | 1 | 30.8× | 0.035 | APC2 |
| proteasome-mediated ubiquitin-dependent protein catabolic process | 1 | 26.1× | 0.040 | APC2 |
| nervous system development | 1 | 23.0× | 0.043 | APC2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SLC25A23 | 0 | 0 |
| APC2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | 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.