Human Gene Module / Chromosome 7 / CADPS2

CADPS2Ca2+-dependent activator protein for secretion 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 13
Rare Variants / Common Variants
24 / 0
Aliases
CADPS2, FLJ40851,  KIAA1591
Associated Syndromes
-
Chromosome Band
7q31.32
Associated Disorders
EPS
Relevance to Autism

Studies have found rare variants in the CADPS2 gene to be associated with autism, although one study found no genetic association in a family-based TDT test (Cisternas et al., 2003).

Molecular Function

The encoded protein has calcium-binding activity and mediates vesicle exocytosis.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CADPS2 (13 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+-dependent activator for secretion protein family Cisternas FA , et al. (2003) Yes -
2 Recent Recommendation Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release Sadakata T , et al. (2007) No -
3 Support Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients Sadakata T , et al. (2007) Yes -
4 Recent Recommendation Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants Sadakata T , et al. (2007) No -
5 Recent Recommendation Voxelwise genome-wide association study (vGWAS) Stein JL , et al. (2010) No -
6 Recent Recommendation Submicroscopic deletion in 7q31 encompassing CADPS2 and TSPAN12 in a child with autism spectrum disorder and PHPV Okamoto N , et al. (2011) No -
7 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
8 Recent Recommendation Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder Vardarajan BN , et al. (2013) No -
9 Recent Recommendation Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients Bonora E , et al. (2014) Yes Epilepsy
10 Recent Recommendation Axonal localization of Ca2+-dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor and neurotrophin-3 release affecting proper development of postnatal mouse cerebellum Sadakata T , et al. (2014) No -
11 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) No -
12 Support Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing Aristidou C , et al. (2017) No -
13 Support - Sheth F et al. (2023) Yes DD, ID
Rare Variants   (24)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - - 27841880 Redin C , et al. (2016)
insT - intron_variant - - - 12659812 Cisternas FA , et al. (2003)
- - translocation Unknown - Simplex 28072833 Aristidou C , et al. (2017)
c.2461C>T p.(=) synonymous_variant - - - 12659812 Cisternas FA , et al. (2003)
c.2405T>C p.Val802Ala missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.2410C>G p.Leu804Val missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.2495G>T p.Arg832Ile missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.2896A>G p.Thr925Ala missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.3013G>A p.Ala1005Thr missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.3163G>A p.Ala1055Thr missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.3334G>A p.Asp1112Asn missense_variant - - - 17380209 Sadakata T , et al. (2007)
c.3599C>T p.Thr1200Met missense_variant - - - 17380209 Sadakata T , et al. (2007)
- - copy_number_loss Familial Maternal Multiplex 24737869 Bonora E , et al. (2014)
- - copy_number_gain Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
c.2539A>C p.Ile847Leu synonymous_variant - - - 12659812 Cisternas FA , et al. (2003)
c.1891G>A p.Asp631Asn missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.983G>A p.Gly328Asp missense_variant Familial Paternal - 12659812 Cisternas FA , et al. (2003)
c.78C>T p.Ala26= synonymous_variant Familial Maternal Simplex 24737869 Bonora E , et al. (2014)
c.1889T>C p.Met630Thr missense_variant Familial Paternal Simplex 24737869 Bonora E , et al. (2014)
c.1933T>G p.Phe645Val missense_variant Familial Maternal Simplex 24737869 Bonora E , et al. (2014)
c.1206C>G p.Ala402= synonymous_variant Familial Paternal Simplex 24737869 Bonora E , et al. (2014)
c.3337G>A p.Asp1113Asn missense_variant Familial Maternal Simplex 24737869 Bonora E , et al. (2014)
c.3409G>A p.Val1137Met missense_variant Familial Maternal Simplex 24737869 Bonora E , et al. (2014)
c.3262G>A p.Asp1088Asn missense_variant Familial Paternal Multiplex 24737869 Bonora E , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

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

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

Reports Added
[New Scoring Scheme]
1/1/2017
4
icon
4

Decreased from 4 to 4

Description

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

Reports Added
[Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing.2017]
10/1/2016
4
icon
4

Decreased from 4 to 4

Description

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

Reports Added
[The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

Reports Added
[Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+dependent activator for secretion protein family.2003] [Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release.2007] [Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients.2007] [Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants.2007] [Voxelwise genome-wide association study (vGWAS).2010] [Submicroscopic deletion in 7q31 encompassing CADPS2 and TSPAN12 in a child with autism spectrum disorder and PHPV.2011] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder.2013] [Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients.2014] [Axonal localization of Ca2+dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor a...2014]
4/1/2014
No data
icon
4

Increased from No data to 4

Description

There is minimal evidence for CADPS2 in autism. The gene is within the AUTS1 linkage region and also lies within a 750-kb de novo deletion identified in a single autism patient (Szatmari et al. 2007). In one study of 252 patients, seven nonsynonymous SNPs were identified that were not present in 217 controls (Sadakata et al. 2007). In addition, there is conflicting evidence regarding aberrant splicing of the gene in patients with autism compared to controls. While one study reported transcripts that skip exon 3 only in patients (4/16 compared to 0/24 controls), another study reports exon-3 skipping transcripts in both cases (5/41) and controls (6/39).

Reports Added
[Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients.2014]
Krishnan Probability Score

Score 0.49636506345954

Ranking 2616/25841 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 0.99777895404242

Ranking 1288/18225 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 0.95025363244724

Ranking 18419/18665 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
Larsen Cumulative Evidence Score

Score 13

Ranking 149/461 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.
Original Source
Zhang D Score

Score 0.47119473109755

Ranking 737/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
MEGF10 multiple EGF-like-domains 10 Human Protein Binding 84466 Q96KG7
UBE2D2 ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, yeast) Human Protein Binding 7322 P62837
UBE2D3 ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast) Human Protein Binding 7323 P61077
UBE2D4 Ubiquitin-conjugating enzyme E2 D4 Human Protein Binding 51619 Q9Y2X8
UBE2E1 ubiquitin-conjugating enzyme E2E 1 Human Protein Binding 7324 P51965
UBE2E3 ubiquitin-conjugating enzyme E2E 3 Human Protein Binding 10477 Q969T4
UBE2N ubiquitin-conjugating enzyme E2N Human Protein Binding 7334 P61088
UBE2U Ubiquitin-conjugating enzyme E2 U Human Protein Binding 148581 Q5VVX9
UBE2W ubiquitin-conjugating enzyme E2W (putative) Human Protein Binding 55284 Q96B02
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