Holoprosencephaly 11
diseaseOn this page
Also known as CDON holoprosencephalyholoprosencephaly caused by mutation in CDONholoprosencephaly type 11HPE11
Summary
Holoprosencephaly 11 (MONDO:0013642) is a disease caused by CDON (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: CDON (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 476
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | holoprosencephaly 11 |
| Mondo ID | MONDO:0013642 |
| OMIM | 614226 |
| DOID | DOID:0110877 |
| UMLS | C3280215 |
| MedGen | 481845 |
| GARD | 0024938 |
| Is cancer (heuristic) | no |
Also known as: CDON holoprosencephaly · holoprosencephaly 11 · holoprosencephaly caused by mutation in CDON · holoprosencephaly type 11 · HPE11
Data availability: 476 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › holoprosencephaly › holoprosencephaly 11
Related subtypes (16): holoprosencephaly 3, holoprosencephaly 4, holoprosencephaly 2, holoprosencephaly 1, holoprosencephaly 6, holoprosencephaly 8, holoprosencephaly 7, chromosome 1q41-q42 deletion syndrome, microform holoprosencephaly, lobar holoprosencephaly, alobar holoprosencephaly, holoprosencephaly 13, X-linked, holoprosencephaly 14, holoprosencephaly 12 with or without pancreatic agenesis, semilobar holoprosencephaly, holoprosencephaly 10
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
476 retrieved; paginated sample, class counts are floors:
242 uncertain significance, 99 likely benign, 81 benign, 33 conflicting classifications of pathogenicity, 18 benign/likely benign, 2 pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 30748 | NM_001378964.1(CDON):c.2339T>A (p.Val780Glu) | CDON | Pathogenic | no assertion criteria provided |
| 30749 | NM_001378964.1(CDON):c.2368A>G (p.Thr790Ala) | CDON | Pathogenic | no assertion criteria provided |
| 30747 | NM_001378964.1(CDON):c.2065C>G (p.Pro689Ala) | CDON | Likely pathogenic | criteria provided, single submitter |
| 1358028 | NM_001378964.1(CDON):c.2624G>A (p.Ser875Asn) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1398759 | NM_001378964.1(CDON):c.3100G>A (p.Gly1034Arg) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1491551 | NM_001378964.1(CDON):c.2770A>G (p.Lys924Glu) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1496647 | NM_001378964.1(CDON):c.1025A>G (p.Asn342Ser) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 193724 | NM_001378964.1(CDON):c.1855G>C (p.Asp619His) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2072075 | NM_001378964.1(CDON):c.173G>A (p.Arg58His) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2108114 | NM_001378964.1(CDON):c.3761C>T (p.Pro1254Leu) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2144121 | NM_001378964.1(CDON):c.3560G>A (p.Arg1187His) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2147303 | NM_001378964.1(CDON):c.101A>C (p.Glu34Ala) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2153581 | NM_001378964.1(CDON):c.3258T>A (p.His1086Gln) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2386666 | NM_001378964.1(CDON):c.2383G>A (p.Val795Ile) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2439889 | NM_001378964.1(CDON):c.644C>G (p.Pro215Arg) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2730050 | NM_001378964.1(CDON):c.1619G>T (p.Arg540Ile) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2737484 | NM_001378964.1(CDON):c.3197_3198insATTGAATGGGAGCCTAAA (p.Leu1065_Asn1066insLysLeuAsnGlySerLeu) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2850732 | NM_001378964.1(CDON):c.2492A>G (p.His831Arg) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 303503 | NM_001378964.1(CDON):c.2159-14G>A | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 303510 | NM_001378964.1(CDON):c.1847G>A (p.Arg616Gln) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 303511 | NM_001378964.1(CDON):c.1826A>G (p.Asn609Ser) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3141684 | NM_001378964.1(CDON):c.2854G>A (p.Val952Met) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3652383 | NM_001378964.1(CDON):c.2496T>G (p.Ile832Met) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 422386 | NM_001378964.1(CDON):c.791C>A (p.Pro264Gln) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 539750 | NM_001378964.1(CDON):c.1310G>A (p.Arg437His) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 702448 | NM_001378964.1(CDON):c.1069C>A (p.Arg357=) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 707303 | NM_001378964.1(CDON):c.2567A>G (p.Asn856Ser) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 842607 | NM_001378964.1(CDON):c.1387T>C (p.Ser463Pro) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 877739 | NM_001378964.1(CDON):c.3754G>C (p.Asp1252His) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 877741 | NM_001378964.1(CDON):c.3602G>A (p.Gly1201Asp) | CDON | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 7 · 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 |
|---|---|---|---|---|
| CDON | Definitive | Autosomal dominant | holoprosencephaly 11 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CDON | Orphanet:220386 | Semilobar holoprosencephaly |
| CDON | Orphanet:280195 | Septopreoptic holoprosencephaly |
| CDON | Orphanet:280200 | Microform holoprosencephaly |
| CDON | Orphanet:93924 | Lobar holoprosencephaly |
| CDON | Orphanet:93925 | Alobar holoprosencephaly |
| CDON | Orphanet:93926 | Midline interhemispheric variant of holoprosencephaly |
| CDON | Orphanet:95496 | Pituitary stalk interruption 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 |
|---|---|---|---|---|---|
| CDON | HGNC:17104 | ENSG00000064309 | Q4KMG0 | Cell adhesion molecule-related/down-regulated by oncogenes | gencc,clinvar |
| ACRV1 | HGNC:127 | ENSG00000134940 | P26436 | Acrosomal protein SP-10 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CDON | Cell adhesion molecule-related/down-regulated by oncogenes | Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 1 | 14.6× | 0.135 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CDON | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| ACRV1 | Other/Unknown | no | LY6_UPA_recep-like, Acrosomal_SP-10-like |
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 |
|---|---|
| calcaneal tendon | 1 |
| ganglionic eminence | 1 |
| ventricular zone | 1 |
| left testis | 1 |
| right testis | 1 |
| testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CDON | 222 | ubiquitous | marker | ventricular zone, ganglionic eminence, calcaneal tendon |
| ACRV1 | 145 | tissue_specific | marker | left testis, right testis, testis |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ACRV1 | 1,433 |
| CDON | 1,065 |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CDON | Q4KMG0 | 3 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ACRV1 | P26436 | 62.66 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Ligand-receptor interactions | 1 | 1427.5× | 0.005 | CDON |
| Activation of SMO | 1 | 634.4× | 0.006 | CDON |
| Myogenesis | 1 | 380.7× | 0.006 | CDON |
| Signaling by Hedgehog | 1 | 184.2× | 0.009 | CDON |
| Hedgehog ‘on’ state | 1 | 158.6× | 0.009 | CDON |
| Developmental Biology | 1 | 14.5× | 0.081 | CDON |
| Signal Transduction | 1 | 10.2× | 0.098 | CDON |
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 skeletal muscle tissue development | 1 | 1404.3× | 0.004 | CDON |
| embryonic retina morphogenesis in camera-type eye | 1 | 1203.7× | 0.004 | CDON |
| embryonic body morphogenesis | 1 | 1053.2× | 0.004 | CDON |
| skeletal muscle satellite cell differentiation | 1 | 1053.2× | 0.004 | CDON |
| positive regulation of small GTPase mediated signal transduction | 1 | 1053.2× | 0.004 | CDON |
| negative regulation of biomineral tissue development | 1 | 766.0× | 0.004 | CDON |
| cellular response to vitamin D | 1 | 766.0× | 0.004 | CDON |
| myoblast fusion | 1 | 300.9× | 0.008 | CDON |
| central nervous system neuron differentiation | 1 | 300.9× | 0.008 | CDON |
| positive regulation of neuroblast proliferation | 1 | 290.6× | 0.008 | CDON |
| cell fate specification | 1 | 263.3× | 0.008 | CDON |
| lens development in camera-type eye | 1 | 187.2× | 0.010 | CDON |
| neuroblast proliferation | 1 | 183.2× | 0.010 | CDON |
| cerebral cortex development | 1 | 102.8× | 0.016 | CDON |
| positive regulation of neuron differentiation | 1 | 99.1× | 0.016 | CDON |
| smoothened signaling pathway | 1 | 90.6× | 0.016 | CDON |
| anterior/posterior pattern specification | 1 | 90.6× | 0.016 | CDON |
| negative regulation of canonical Wnt signaling pathway | 1 | 58.9× | 0.023 | CDON |
| cell-cell adhesion | 1 | 50.8× | 0.025 | CDON |
| positive regulation of MAPK cascade | 1 | 40.3× | 0.030 | CDON |
| nervous system development | 1 | 23.0× | 0.049 | CDON |
| cell adhesion | 1 | 18.7× | 0.057 | CDON |
| spermatogenesis | 1 | 17.6× | 0.058 | ACRV1 |
| positive regulation of transcription by RNA polymerase II | 1 | 7.4× | 0.130 | CDON |
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 |
|---|---|---|
| CDON | 0 | 0 |
| ACRV1 | 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 | 1 | CDON |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | ACRV1 |
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) |
|---|---|---|
| CDON | 0 | — |
| ACRV1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.