Human Gene Module / Chromosome 11 / CDON

CDONcell adhesion associated, oncogene regulated

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
11 / 0
Aliases
CDON, CDO1,  HPE11,  ORCAM, CDON
Associated Syndromes
-
Chromosome Band
11q24.2
Associated Disorders
DD/NDD, ADHD
Relevance to Autism

Genome-wide investigation of tandem repeats in 17,231 genomes of families with autism from the Autism Speaks MSSNG project and the Simons Simplex Collection in Trost et al., 2020 identified a rare tandem repeat expansion in the CDON gene (chr11:126063945-126066092 (AAGAGGTGGCAGTATT)) in six unrelated ASD probands. This tandem repeat in CDON was observed in more than 0.1% of ASD-affected individuals in this cohort and had a frequency less than 0.1% in unaffected siblings, 1000 Genomes, and 1,612 additional population controls from GTEx and the Mayo Clinic Biobank.

Molecular Function

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. Heterozygous mutations in this gene are associated with holoprosencephaly (holoprosencephaly-11; OMIM 614226).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CDON (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genome-wide detection of tandem DNA repeats that are expanded in autism Trost B et al. (2020) Yes DD, ADHD
2 Support - Woodbury-Smith M et al. (2022) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - minisatellite Unknown - Simplex 32717741 Trost B et al. (2020)
- - minisatellite Unknown - Unknown 32717741 Trost B et al. (2020)
c.1846C>G p.Arg616Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2644G>A p.Val882Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.497-2A>G - splice_site_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3524G>A p.Ser1175Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3544C>T p.Pro1182Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2034A>G p.Thr678%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.202T>C p.Leu68%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1373G>A p.Arg458Gln missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1372C>T p.Arg458Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.49470049687146

Ranking 3482/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 3.0490687994448E-12

Ranking 17277/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.90432809824059

Ranking 6836/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.43949359939282

Ranking 1030/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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