CADPS2

protein-coding

calcium dependent secretion activator 2, the group of Pleckstrin homology domain containing|C2 domain containing

Gene summary

This gene encodes a member of the calcium-dependent activator of secretion (CAPS) protein family, which are calcium binding proteins that regulate the exocytosis of synaptic and dense-core vesicles in neurons and neuroendocrine cells. Mutations in this gene may contribute to autism susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

MANE transcript

NM_017954.11

Inheritance

—

ClinVar variants

U:166B:21

Top phenotype

CADPS2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr7:122,318,411-122,886,759

External References & Databases

Ensembl (ENSG00000081803)

Transcript & Mutation Effects

hg38 • Region Span ~568.3 kb

Loading mutation effect viewer...

GenCC 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 CADPS2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 269

not providedTotal: 21

CADPS2-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017954.11. 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			4 clinvar	6 clinvar	4 clinvar	14
missense			155 clinvar	8 clinvar	3 clinvar	166
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	166	14	7	187

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 82 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017954.11	RefSeq	NP_060424.9	30	MANE Select
ENST00000449022.7	Ensembl	ENSP00000398481.2	30	MANE Select
NM_001009571.4	RefSeq	NP_001009571.2	28	Standard
NM_001167940.2	RefSeq	NP_001161412.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular response to starvation
protein transport
synaptic vesicle priming
positive regulation of exocytosis
dense core granule exocytosis

Molecular Function

lipid binding
metal ion binding

Cellular Component

nucleoplasm
cell junction
cytoplasmic vesicle membrane
presynaptic membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000449022
Coding exons: 30
Length: 568333
Individuals with no LoFs: 124642
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 124679
p: 0.000148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	561	639	0.878	0.0000320	8445
Missense (PolyPhen)		128	183.71	0.69676		2391
Synonymous	0.570	222	233	0.953	0.0000120	2375
Loss of Function	6.03	16	70.7	0.226	0.00000358	918

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000067	0.000065	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00017	0.00017	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.000034	0.000033	rare
Other	0.00019	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

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 neurotrophin release from granule cells leading to regulate cell differentiation and survival during cerebellar development. May specifically mediate the Ca(2+)- dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.123

Intolerance Scores

RVIS EVS: -0.66
RVIS percentile EVS: 16.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.734

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium