CDON
protein-codingcell adhesion associated, oncogene regulated, the group of Fibronectin type III domain containing|I-set domain containing
Gene summary
This gene encodes a cell surface receptor that is a member of the immunoglobulin superfamily. The encoded protein contains three fibronectin type III domains and five immunoglobulin-like C2-type domains. This protein is a member of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells and positively regulates myogenesis. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~107.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013642
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0019828
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0013642
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0013642
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0013642
Submitter: Illumina
The CDON gene is located on chromosome 11 at 11q24.2 and encodes the cell adhesion associated, oncogene regulated protein. This protein, which is a member of the immunoglobulin superfamily, is highly expressed during embryonic development and functions as part of a cell surface receptor complex in the Sonic hedgehog signalling pathway. The CDON gene was first reported in relation to an autosomal dominant form of holoprosencephaly in 2011 (21802063: Bae et al. 2011). At least five missense variants and one stop gained variant have been reported. Evidence supporting this gene-disease relationship includes case level data and experimental data. Variants in the CDON gene have been reported in at least six probands from three publications (21802063: Bae et al. 2011; 26728615: Jones et al. 2016; 26529631: Bashamboo et al. 2016). This gene-disease relationship is supported by expression studies that are consistent with the disease (10974670: Mulieri et al. 2000) and in vitro experimental data demonstrating physical protein interaction with the SHH gene, which is also associated with a holoprosencephaly phenotype (21802063: Bae et al. 2011). A homozygous mouse model showed facial defects of microform holoprosencephaly along with increased neonatal mortality, and reduction of CDON mRNA in the embryos of zebrafish and chick recapitulated the optic anomalies of the disease phenotypic spectrum (12620190: Cole et al. 2003; 25001599: Cardozo et al. 2014). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Endocrine; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CDON variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001378964.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | 93 | 8 | 109 | ||
| missense | 3 | 1 | 324 | 63 | 3 | 394 |
| nonsense | 1 | 10 | 11 | |||
| start loss | 0 | |||||
| frameshift | 1 | 19 | 20 | |||
| splice donor/acceptor (+/-2bp) | 14 | 14 | ||||
| Total | 3 | 3 | 375 | 156 | 11 | 548 |
Highest pathogenic variant AF is 0.0000068456297
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001365893.1 | 19 | MANE Select | |
| Ensembl | ENSP00000432901.2 | 19 | MANE Select | |
| RefSeq | NP_001230526.1 | 19 | Standard | |
| RefSeq | NP_001428090.1 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cdon | Danio rerio | Structure: optic fissure Quality: closure incomplete abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hedgehog signaling pathway - Homo sapiens (human)
- Ectoderm Differentiation
- MECP2 and Associated Rett Syndrome
- Hedgehog Signaling Pathway
- Developmental Biology
Biological Process
- cell fate specification
- lens development in camera-type eye
- cell adhesion
- smoothened signaling pathway
- myoblast fusion
Molecular Function
- protein binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392693
- Coding exons
- 19
- Length
- 107540
- Individuals with no LoFs
- 125623
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 125
- Defined
- 125748
- p
- 0.000497
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.209 | 705 | 721 | 0.978 | 0.0000399 | 8375 |
| Missense (PolyPhen) | 224 | 253.34 | 0.88417 | 2972 | ||
| Synonymous | -0.398 | 278 | 270 | 1.03 | 0.0000161 | 2616 |
| Loss of Function | 2.91 | 33 | 56.6 | 0.583 | 0.00000327 | 650 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00060 | 0.00060 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00077 | 0.00076 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Holoprosencephaly 11 (HPE11) [MIM:614226]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. {ECO:0000269|PubMed:21802063}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.906
- RVIS EVS
- 0.84
- RVIS percentile EVS
- 88.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.426
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |