Human Gene Module / Chromosome 3 / CADM2

CADM2Cell adhesion molecule 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
4 / 1
Aliases
CADM2, IGSF4D,  NECL3,  Necl-3,  SynCAM 2,  synCAM2
Associated Syndromes
-
Chromosome Band
3p12.1
Associated Disorders
-
Relevance to Autism

CADM2 was identified in an ASD candidate gene via homozygous haplotype mapping analysis performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs) (Casey et al., 2012).

Molecular Function

Adhesion molecule that engages in homo- and heterophilic interactions with the other nectin-like family members, leading to cell aggregation. Important for synapse organization, providing regulated trans-synaptic adhesion.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CADM2 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions Thomas LA , et al. (2008) No -
2 Primary A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder Casey JP , et al. (2011) Yes -
3 Positive Association Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis Namjou B , et al. (2014) Yes -
4 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
5 Support - Tuncay IO et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.497T>C p.Ile166Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1147G>A p.Val383Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - intergenic_variant Familial Both parents Simplex 35190550 Tuncay IO et al. (2022)
c.1193C>A p.Thr398Lys missense_variant De novo - - 31452935 Feliciano P et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.61+191215G>A;c.61+191216G>A Minor allele, A intron_variant - - - 25477900 Namjou B , et al. (2014)
SFARI Gene score
2

Strong Candidate

CADM2 was identified in an ASD candidate gene via homozygous haplotype mapping analysis performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs) (Casey et al., 2012). An intronic SNP in the CADM2 gene showed association to ASD (P-value of 4.34E-05; false discovery rate (FDR) q-value of 0.0004) in a Phe-WAS case-control analysis (Namjou et al., 2014).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

CADM2 was identified in an ASD candidate gene via homozygous haplotype mapping analysis performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs) (Casey et al., 2012). An intronic SNP in the CADM2 gene showed association to ASD (P-value of 4.34E-05; false discovery rate (FDR) q-value of 0.0004) in a Phe-WAS case-control analysis (Namjou et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

CADM2 was identified in an ASD candidate gene via homozygous haplotype mapping analysis performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs) (Casey et al., 2012). An intronic SNP in the CADM2 gene showed association to ASD (P-value of 4.34E-05; false discovery rate (FDR) q-value of 0.0004) in a Phe-WAS case-control analysis (Namjou et al., 2014).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

CADM2 was identified in an ASD candidate gene via homozygous haplotype mapping analysis performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs) (Casey et al., 2012). An intronic SNP in the CADM2 gene showed association to ASD (P-value of 4.34E-05; false discovery rate (FDR) q-value of 0.0004) in a Phe-WAS case-control analysis (Namjou et al., 2014).

Krishnan Probability Score

Score 0.4986613543512

Ranking 2229/25841 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 0.98466890956328

Ranking 1987/18225 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 0.94777522529017

Ranking 17413/18665 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 0.42823371133499

Ranking 1135/20870 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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