Human Gene Module / Chromosome 21 / DSCAM

DSCAMDown syndrome cell adhesion molecule

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
15 / 1
Aliases
DSCAM, CHD2,  CHD2-42,  CHD2-52
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
21q22.2
Associated Disorders
-
Relevance to Autism

Three de novo loss-of-function variants in the DSCAM gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD)

Reports related to DSCAM (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
2 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
3 Recent recommendation Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA. Turner TN , et al. (2016) Yes -
4 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
5 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) No -
6 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
7 Positive association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ... Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2356+2T>G - splice_site_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.4132+2T>A - splice_site_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.5653dupA p.Met1885fs frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.4020_4021insTA p.Asn1341_Gly1342delinsTer frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
- - copy_number_loss Familial Maternal Simplex 26749308 Turner TN , et al. (2016)
c.1067del p.Pro356LeufsTer5 frameshift_variant De novo - - 27824329 Wang T , et al. (2016)
c.4885C>T p.Arg1629Ter stop_gained De novo - - 27824329 Wang T , et al. (2016)
c.4859G>A p.Arg1620Gln missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.4420G>T p.Glu1474Ter stop_gained Familial Maternal - 27824329 Wang T , et al. (2016)
c.596C>T p.Thr199Met missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.4859G>A p.Arg1620Gln missense_variant Unknown Not maternal - 27824329 Wang T , et al. (2016)
c.596C>T p.Thr199Met missense_variant Unknown - - 27824329 Wang T , et al. (2016)
c.5652_5653delAAinsAAA p.Met1885AsnfsTer13 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.4020delCinsCTA p.Asn1341Ter frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.1533_1537del p.Lys511fs frameshift_variant Unknown - Multiplex 28263302 C Yuen RK , et al. (2017)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.3851-2266A>G;c.3143-2266A>G - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
1

High Confidence

Three de novo LoF variants in the DSCAM gene were identified in ASD probands from the Simons Simplex Collection (PMID 25363768), while a fourth de novo LoF variant in this gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). Two additional de novo LoF variants were identified in Chinese ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016.

1

High Confidence

See all Category 1 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.

04-01-2017
1

Initial score established: 1

Description

Three de novo LoF variants in the DSCAM gene were identified in ASD probands from the Simons Simplex Collection (PMID 25363768), while a fourth de novo LoF variant in this gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). Two additional de novo LoF variants were identified in Chinese ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016.

CNVs associated with DSCAM(1 CNVs)
21q22.2 5 Deletion-Duplication 11  /  22
Animal Models associated with DSCAM(6 Models)
DSCAM_1_SP-del17_HM Genetic
DSCAM_2_SP-del17_HM_Thy1-YFP Genetic
DSCAM_7_KO_HM_hybrid Genetic
DSCAM_7_KO_HM_pure Genetic
DSCAM_8_KO_HT_hybrid Genetic
DSCAM_8_KO_HT_pure Genetic
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
DCC Netrin receptor DCC Mouse Protein Binding 13176 P70211
LGR4 leucine-rich repeat containing G protein-coupled receptor 4 Human Protein Binding 55366 Q59ER8
Netrin-1 Netrin-1 Mouse Direct Regulation 18208 O09118
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