CADM1cell adhesion molecule 1
Autism Reports / Total Reports
5 / 10Rare Variants / Common Variants
6 / 0Aliases
CADM1, BL2, ST17, IGSF4, NECL2, RA175, TSLC1, IGSF4A, Necl-2, SYNCAM, sgIGSF, sTSLC-1, synCAM1, MGC51880, MGC149785, DKFZp686F1789, CADM1Associated Syndromes
-Chromosome Band
11q23.3Associated Disorders
IDRelevance 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.
External Links
SFARI Genomic Platforms
Reports related to CADM1 (10 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 | - |
| 10 | Support | - | Alonso-Gonzalez A et al. (2021) | Yes | - |
Rare Variants (6)
| 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.391C>T | p.Pro131Ser | missense_variant | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
| 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
2
Strong Candidate
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: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 2
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).
1/1/2021
3
3
Decreased from 3 to 3
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).
10/1/2019
4
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
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
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
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.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
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 |