CADPS
protein-codingcalcium dependent secretion activator, the group of Pleckstrin homology domain containing
Gene summary
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). Alternative splicing has been observed at this locus and three variants, encoding distinct isoforms, are described. [provided by RefSeq, Aug 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~477.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CADPS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003716.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 23 | 3 | 29 | ||
| missense | 142 | 3 | 145 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 154 | 26 | 3 | 183 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003707.2 | 30 | MANE Select | |
| Ensembl | ENSP00000373215.4 | 30 | MANE Select | |
| RefSeq | NP_001424820.1 | 28 | Standard | |
| RefSeq | NP_001425276.1 | 31 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- exocytosis
- protein transport
- synaptic vesicle exocytosis
- dense core granule exocytosis
Molecular Function
- protein binding
- lipid binding
- protein kinase binding
- metal ion binding
Cellular Component
- cytosol
- cell junction
- cytoplasmic vesicle membrane
- presynapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000383710
- Coding exons
- 30
- Length
- 477033
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125747
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.10 | 525 | 767 | 0.685 | 0.0000446 | 8911 |
| Missense (PolyPhen) | 17 | 34.822 | 0.48819 | 321 | ||
| Synonymous | -1.44 | 319 | 288 | 1.11 | 0.0000173 | 2521 |
| Loss of Function | 5.64 | 24 | 77.6 | 0.309 | 0.00000432 | 862 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000092 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates catecholamine loading of DCVs. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-binding protein that acts at prefusion step following ATP-dependent priming and participates in DCVs-membrane fusion. However, it may also participate in small clear synaptic vesicles (SVs) exocytosis and it is unclear whether its function is related to Ca(2+) triggering (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.384
- RVIS EVS
- -1.35
- RVIS percentile EVS
- 4.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.373
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |