Human Gene Module / Chromosome 11 / CADM1

CADM1cell adhesion molecule 1

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 9
Rare Variants / Common Variants
5 / 0
Aliases
CADM1, BL2,  ST17,  IGSF4,  NECL2,  RA175,  TSLC1,  IGSF4A,  Necl-2,  SYNCAM,  sgIGSF,  sTSLC-1,  synCAM1,  MGC51880,  MGC149785,  DKFZp686F1789,  CADM1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
11q23.3
Associated Disorders
ID
Relevance to Autism

Rare variants in the CADM1 gene have been identified with autism (Zhiling et al., 2008).

Molecular Function

The gene encodes a brain-specific, immunoglobulin domain-containing protein. It binds to intracellular PDZ-domain proteins and functions as a homophilic cell adhesion molecule at the synapse.

Reports related to CADM1 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited SynCAM, a synaptic adhesion molecule that drives synapse assembly. Biederer T , et al. (2002) No -
2 Recent Recommendation Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Samuels BA , et al. (2007) No -
3 Recent Recommendation Gene expression patterns in visual cortex during the critical period: synaptic stabilization and reversal by visual deprivation. Lyckman AW , et al. (2008) No -
4 Recent Recommendation Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions. Thomas LA , et al. (2008) No -
5 Primary Mutations in the gene encoding CADM1 are associated with autism spectrum disorder. Zhiling Y , et al. (2008) Yes -
6 Recent Recommendation Autism spectrum disorder is related to endoplasmic reticulum stress induced by mutations in the synaptic cell adhesion molecule, CADM1. Fujita E , et al. (2011) No -
7 Support Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders. Nava C , et al. (2013) Yes ID
8 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Doan RN , et al. (2016) Yes -
9 Support Clinical utility of exome sequencing in individuals with large homozygous regions detected by chromosomal microarray analysis. Prasad A , et al. (2018) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G>T - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.752A>C p.Tyr251Ser missense_variant - - - 29554876 Prasad A , et al. (2018)
- - copy_number_loss Familial Paternal Unknown 23632794 Nava C , et al. (2013)
c.739C>A p.His246Asn missense_variant Familial Maternal Multiplex 18957284 Zhiling Y , et al. (2008)
c.755A>C p.Tyr251Ser missense_variant Familial Paternal Multiplex 18957284 Zhiling Y , et al. (2008)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Single study finding 2 rare variants (PMID: 18957284). No rigorous screening of controls. Mouse knock-out shows impairment of social and emotional behaviors (PMID: 20450890).

Score Delta: Decreased from 4 to 3

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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Single study finding 2 rare variants (PMID: 18957284). No rigorous screening of controls. Mouse knock-out shows impairment of social and emotional behaviors (PMID: 20450890).

Reports Added
[New Scoring Scheme]
10/1/2016
4
icon
4

Decreased from 4 to 4

Description

Single study finding 2 rare variants (PMID: 18957284). No rigorous screening of controls. Mouse knock-out shows impairment of social and emotional behaviors (PMID: 20450890).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

Single study finding 2 rare variants (PMID: 18957284). No rigorous screening of controls. Mouse knock-out shows impairment of social and emotional behaviors (PMID: 20450890).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Single study finding 2 rare variants (PMID: 18957284). No rigorous screening of controls. Mouse knock-out shows impairment of social and emotional behaviors (PMID: 20450890).

Krishnan Probability Score

Score 0.59459318421919

Ranking 452/25841 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.
ExAC Score

Score 0.99438640410443

Ranking 1574/18225 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
Sanders TADA Score

Score 0.93017780819995

Ranking 11360/18665 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).
Larsen Cumulative Evidence Score

Score 8

Ranking 219/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.091911982237282

Ranking 6295/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
BMI1 BMI1 polycomb ring finger oncogene Human DNA Binding 648 P35226
Cadm2 cell adhesion molecule 2 Rat Protein Binding 360687 Q1WIM2
CRTAM cytotoxic and regulatory T cell molecule Human Protein Binding 56253 O95727
Epb4.1l2 erythrocyte protein band 4.1-like 2 Mouse Protein Binding 13822 O70318
EPB41L3 erythrocyte membrane protein band 4.1-like 3 Human Protein Binding 23136 Q9Y2J2
Erbb3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) Mouse Protein Binding 13867 Q61526
F2rl2 coagulation factor II (thrombin) receptor-like 2 Mouse Protein Binding 14064 O08675
KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Human Protein Binding 3815 P10721
MPP1 membrane protein, palmitoylated 1, 55kDa Human Protein Binding 4354 Q96Q89
MPP2 membrane protein, palmitoylated 2 (MAGUK p55 subfamily member 2) Human Protein Binding 4355 Q14168
MPP3 membrane protein, palmitoylated 3 (MAGUK p55 subfamily member 3) Human Protein Binding 4356 Q13368
PSMA6 proteasome (prosome, macropain) subunit, alpha type, 6 Human Protein Binding 5687 P60900
SPPL2B signal peptide peptidase like 2B Human Protein Binding 56928 Q8TCT7
St8sia2 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 Mouse Protein Modification 20450 O35696
ST8SIA4 CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase Chinese hamster Protein Modification 100689217 Q64690
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