Human Gene Module / Chromosome 3 / CADPS

CADPScalcium dependent secretion activator

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 5
Rare Variants / Common Variants
4 / 1
Aliases
CADPS, CADPS1,  CAPS,  CAPS1,  UNC-31
Associated Syndromes
-
Chromosome Band
3p14.2
Associated Disorders
-
Relevance to Autism

An intronic SNP in the CADPS gene (SNP ID rs1452075) was the index variant for a locus that demonstrated significant association with ASD in a genome-wide meta-analysis of cases and controls (P = 2.1E-07); multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD and educational attainment showed that this locus reached genome-wide significance (P = 3.17E-09) (Grove et al., 2019).

Molecular Function

This gene encodes a novel neural/endocrine-specific cytosolic and peripheral membrane protein required for the Ca2+-regulated exocytosis of secretory vesicles. The protein acts at a stage in exocytosis that follows ATP-dependent priming, which involves the essential synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CADPS (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Genome-wide association study identifies 74 loci associated with educational attainment Okbay A , et al. (2016) No -
2 Primary Identification of common genetic risk variants for autism spectrum disorder Grove J , et al. (2019) Yes -
3 Support Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing Bruel AL , et al. (2019) No -
4 Support - Sitbon J et al. (2022) No -
5 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.2555G>A p.Arg852Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3842T>C p.Leu1281Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1716G>A p.Leu572%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1753+1G>T - splice_site_variant - Both parents - 31231135 Bruel AL , et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.2707-1723G>A;c.2638-2942G>A;c.2758-2942G>A - intron_variant - - - 30804558 Grove J , et al. (2019)
SFARI Gene score
2

Strong Candidate

An intronic SNP in the CADPS gene (SNP ID rs1452075) was the index variant for a locus that demonstrated significant association with ASD in a genome-wide meta-analysis of cases and controls (P = 2.1E-07); multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD and educational attainment (from Okbay et al., 2016) showed that this locus reached genome-wide significance (P = 3.17E-09) (Grove et al., 2019).

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

An intronic SNP in the CADPS gene (SNP ID rs1452075) was the index variant for a locus that demonstrated significant association with ASD in a genome-wide meta-analysis of cases and controls (P = 2.1E-07); multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD and educational attainment (from Okbay et al., 2016) showed that this locus reached genome-wide significance (P = 3.17E-09) (Grove et al., 2019).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

An intronic SNP in the CADPS gene (SNP ID rs1452075) was the index variant for a locus that demonstrated significant association with ASD in a genome-wide meta-analysis of cases and controls (P = 2.1E-07); multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD and educational attainment (from Okbay et al., 2016) showed that this locus reached genome-wide significance (P = 3.17E-09) (Grove et al., 2019).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

An intronic SNP in the CADPS gene (SNP ID rs1452075) was the index variant for a locus that demonstrated significant association with ASD in a genome-wide meta-analysis of cases and controls (P = 2.1E-07); multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD and educational attainment (from Okbay et al., 2016) showed that this locus reached genome-wide significance (P = 3.17E-09) (Grove et al., 2019).

Reports Added
[Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing.2019]
1/1/2019
icon
4

Increased from to 4

Description

An intronic SNP in the CADPS gene (SNP ID rs1452075) was the index variant for a locus that demonstrated significant association with ASD in a genome-wide meta-analysis of cases and controls (P = 2.1E-07); multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD and educational attainment (from Okbay et al., 2016) showed that this locus reached genome-wide significance (P = 3.17E-09) (Grove et al., 2019).

Krishnan Probability Score

Score 0.61538834787222

Ranking 119/25841 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 0.052816467531474

Ranking 8502/18225 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 0.94897911366489

Ranking 17904/18665 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 0.24124246842198

Ranking 3606/20870 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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