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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

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+dependent activator for secretion protein family.
ASD
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients.
ASD
Support
Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing.
ID
Support
The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.
DD, dysmorphic features
Recent Recommendation
Submicroscopic deletion in 7q31 encompassing CADPS2 and TSPAN12 in a child with autism spectrum disorder and PHPV.
Recent Recommendation
Voxelwise genome-wide association study (vGWAS).
Recent Recommendation
Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants.
Recent Recommendation
Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release.
Recent Recommendation
Axonal localization of Ca2+dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor a...
Recent Recommendation
Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients.
ASD, ID
Epilepsy
Recent Recommendation
Haplotype structure enables prioritization of common markers and candidate genes in autism spectrum disorder.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN037R001 
 missense_variant 
 c.2405T>C 
 p.Ile761Thr 
  
  
  
 GEN037R002 
 missense_variant 
 c.2419G>C 
 p.Val766Leu 
  
  
  
 GEN037R003 
 missense_variant 
 c.2504C>A 
 p.Thr794Asn 
  
  
  
 GEN037R004 
 missense_variant 
 c.2896A>G 
 p.Thr925Ala 
  
  
  
 GEN037R005 
 missense_variant 
 c.3163G>A 
 p.Asp1055Asn 
  
  
  
 GEN037R006 
 missense_variant 
 c.3163G>A 
 p.Asp1055Asn 
  
  
  
 GEN037R007 
 missense_variant 
 c.3334G>A 
 p.Asp1112Asn 
  
  
  
 GEN037R008 
 missense_variant 
 c.3599C>T 
 p.Thr1200Met 
  
  
  
 GEN037R009 
 missense_variant 
 c.983G>A 
 p.Ala297Thr 
 Familial 
 Paternal 
  
 GEN037R010 
 synonymous_variant 
 c.2461C>T 
 p.(=) 
  
  
  
 GEN037R011 
 synonymous_variant 
 c.2539A>C 
 p.(=) 
  
  
  
 GEN037R012 
 intron_variant 
 insT 
  
  
  
  
 GEN037R013 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN037R014 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN037R015 
 missense_variant 
 c.3337G>A 
 p.Asp1113Asn 
 Familial 
 Maternal 
 Simplex 
 GEN037R016 
 missense_variant 
 c.3409G>A 
 p.Val1137Met 
 Familial 
 Maternal 
 Simplex 
 GEN037R017 
 synonymous_variant 
 c.78C>T 
 p.(=) 
 Familial 
 Maternal 
 Simplex 
 GEN037R018 
 synonymous_variant 
 c.1206C>G 
 p.(=) 
 Familial 
 Paternal 
 Simplex 
 GEN037R019 
 missense_variant 
 c.1889T>C 
 p.Met630Thr 
 Familial 
 Paternal 
 Simplex 
 GEN037R020 
 missense_variant 
 c.1933T>G 
 p.Phe645Val 
 Familial 
 Maternal 
 Simplex 
 GEN037R021 
 missense_variant 
 c.3262G>A 
 p.Asp1088Asn 
 Familial 
 Paternal 
 Multiplex 
 GEN037R022 
 translocation 
  
  
 De novo 
  
  
 GEN037R023 
 translocation 
  
  
 Unknown 
  
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
7
Deletion
 2
 
7
Deletion-Duplication
 21
 
7
Deletion
 2
 
7
Deletion
 1
 
7
Deletion
 1
 
7
Deletion
 9
 

Model Summary

CAPS2-mediated neurotrophin release is indispensable for normal cerebellar development and functions, including neuronal differentiation and survival, morphogenesis, synaptic function, and motor learning/control.

References

Type
Title
Author, Year
Primary
Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release.
Additional
Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients.
Additional
CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins.
Additional
Autistic-like behavioral phenotypes in a mouse model with copy number variation of the CAPS2/CADPS2 gene.
Additional
Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice.

M_CADPS2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A pgk-neo cassette flanked by loxP sites replaced the exon 1 of Cadps2.
Allele Type: Targeted (knock-out)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: MS12
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CADPS2_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: A pgk-neo cassette flanked by loxP sites replaced the exon 1 of Cadps2.
Allele Type: Targeted (knock-out)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: MS12
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CADPS2_3_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A 500 bp genomic fragment containing exon 5 was replaced by a loxP-flanked Neo cassette.
Allele Type: Targeted (Knock out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CADPS2_4_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Cre/loxP mediated deletion of exon 3 of Cadps2 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: Not specified
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CADPS2_5_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Cre/loxP mediated deletion of exon 3 of Cadps2 gene.
Allele Type: Targeted (Knock out)
Strain of Origin: Not specified
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CADPS2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Circadian rhythms: timing/phases of locomotor activity1
Decreased
Description: Mutants have deficits in sleep-wake regulation
Exp Paradigm: Locomotor activity under constant dark (DD) conditions
 Home cage behavior: constant dark conditions
 6 weeks
Motor coordination and balance1
Decreased
Description: Mutants have impaired muscle coordination
Exp Paradigm: Rotarod test
 Accelerating rotarod test
 4 weeks
Hyperactivity1
Increased
Description: In males, significantly higher home-cage activity
Exp Paradigm: Locomotor activity over a 6-day period in 12-hr LD cycle, males only
 Open field test
 10-12 weeks
Brain morphology1
Decreased
Description: Abnormal brain interneuron morphology
Exp Paradigm: Immunohistochemistry
 Immunohistochemistry
 4 weeks
Neuronal differentiation and specification in the brain1
Decreased
Description: Mutant mice have abnormal neuronal differentiation and specification
Exp Paradigm: Immunohistochemistry
 Immunohistochemistry
 4 weeks
Dendritic architecture: spine density1
Abnormal
Description: Mutant mice show abnormal Purkinje cell dendrite morphology
Exp Paradigm: Immunohistochemistry
 Immunohistochemistry
 P8
Cerebellar morphology1
Decreased
Description: Mutant mice have abnormal external granule cell layer morphology and differentiation of granule cell neurons
Exp Paradigm: Immunohistochemistry
 Immunohistochemistry
 4 weeks
Synaptic transmission1
Decreased
Description: Mutant mice have deficient short-term plasticity in the PF-PC synapses
Exp Paradigm: Whole-cell voltage-clamp recordings
 Whole-cell patch clamp
 P15-P21
Social interaction1
Decreased
Description: Cadps2 null mice have reduced social interaction
Exp Paradigm: Direct contacts between genotypically identical pairs test, Males tested only
 Reciprocal social interaction test
 4 weeks
Size/growth1
Decreased
Description: Decreased body weight
Exp Paradigm: General observations
 General observations
 Unreported
Response to novelty1
Decreased
Description: Decreased exploration in new environment
Exp Paradigm: Eight-arm radial maze test
 Eight-arm radial maze test
 5 weeks
Anxiety1
Increased
Description: Increased anxiety-related response
Exp Paradigm: Open field test containing a novel object
 Open field test
 4 weeks
Spatial reference memory1
Decreased
Description: Cadps2 null mice have reduced spatial memory assessed in the probe test of the Morris water maze task
Exp Paradigm: Morris water maze with hidden platform; Males tested
 Morris water maze test
 5 weeks
Spatial learning1
Decreased
Description: Cadps2 null mice have significantly reduced spatial learning during the training days of the hidden platform test
Exp Paradigm: Morris water maze with hidden platform; Males tested
 Morris water maze test
 5 weeks
Maternal nurturing1
Decreased
Description: Cadps2 null mice have reduced maternal nurturing
Exp Paradigm: General observations; Adult females only
 General observations
 
Regulation of gene expression1
Decreased
Description: Significantly fewer paralbumin-positive interneurons in the neocortex
Exp Paradigm: Gene Regulation
 Immunohistochemistry
 P17
General characteristics1
 No Change
 Genotypic ratio of progeny from heterozygous parents
 Unreported
Hearing1
 No Change
 Auditory test: movements to sound stimulus
 Unreported
Olfaction1
 No Change
 Buried food test
 Unreported
Vision1
 No Change
 Forepaw reaching test
 Unreported
 Not Reported: Communications, Homeostasis, Immune response, Repetitive behavior, Seizure

M_CADPS2_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Locomotor activity in diurnal cycle2
Increased
Description: Increased activity in the diurnal cycle
Exp Paradigm: Recording of circadian rhythm using wheel-running
 Running wheel test
 8 weeks
Ultrasonic vocalization2
Decreased
Description: Decreased number of ultrasonic vocalizations with decrease apparent in early postnatal stage
Exp Paradigm: Ultrasonic vocalization measurement during dam-pup interaction
 Monitoring ultrasonic vocalizations: maternal separation
 P5-P7
Response to novelty2
Decreased
Description: Decreased response to novelty demonstrated by decreased activity and speed
Exp Paradigm: Open field test containing a novel object
 Open field test
 12 months
Response to novelty1
Decreased
Description: Decreased exploration in new environment
Exp Paradigm: Eight-arm radial maze test
 Eight-arm radial maze test
 5 weeks
Maternal nurturing1
Decreased
Description: Cadps2 het female mice show reduced maternal nurturing
Exp Paradigm: General observations; Adult females
 General observations
 
Protein expression level evidence2
Decreased
Description: Decreased levels of Cadps2-immunopositive bands in protein extracts from cerebellum, hippocampus, neocortex
Exp Paradigm: Cadps2 Protein Expression
 Western blot
 Unreported
Circadian rhythm2
 No Change
 Running wheel test
 2 months
General characteristics1
 No Change
 General observations
 Unreported
Anxiety2
 No Change
 Elevated plus maze test
 Unreported
Anxiety2
 No Change
 Light-dark exploration test: Light-dark exploration test
 Unreported
Fear response2
 No Change
 Open field test
 12 months
Spatial learning1
 No Change
 Morris water maze test: hidden platform trial
 5 weeks
Gene expression1
 No Change
 Immunohistochemistry
 4 weeks
General locomotor activity2
 No Change
 Elevated plus maze test
 12 months
General locomotor activity2
 No Change
 Open field test
 12 months
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 4 weeks
Social interaction2
 No Change
 Reciprocal social interaction test
 Unreported
Social interaction1
 No Change
 Reciprocal social interaction test
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory

M_CADPS2_3_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic transmission1
 No Change
 Whole-cell patch clamp
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

M_CADPS2_4_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Sleep pattern1
Decreased
Description: Mutant mice have shorter sleep pattern period under constant dark conditions
Exp Paradigm: Circadian rhythm recording under constant dark conditions
 Home cage behavior
 8 weeks
Motor coordination and balance1
Decreased
Description: Decreased motor coordination as measured by average number of falls within a 3 min period at 24 rpm
Exp Paradigm: Rotarod test
 Accelerating rotarod test
 2 months
Neuronal differentiation and specification in the brain1
Decreased
Description: There is a transient decrease in the number of calbindin-positive interneurons in the hippocampus at P7 in Cadps2 null mice
 
 P7
Neuronal differentiation and specification in the brain1
Decreased
Description: Cadps2 null mice have reduced parvalbumin-positive interneurons in the neocortex
 
 P17; P21
Dendritic architecture: spine density1
Decreased
Description: Decreased number of dendritiv protrusions and decreased number of spines on dendrites of dentate gyrus
Exp Paradigm: Golgi Staining
 Golgi-Cox staining
 Unreported
Social interaction1
Decreased
Description: Decreased social interaction indicated by reduction in time spent approaching or interacting with stranger mouse cage
Exp Paradigm: open field test containing a stranger mouse
 Open field test
 2 months
Social interaction1
Decreased
Description: Decreased social interaction indicated by no difference in time spent with stranger mouse and empty cage
Exp Paradigm: Three-chamber social interaction test
 Three-chamber social approach test
 2 months
Social interaction1
Decreased
Description: Decreased exploratory activity indicated by reduced activity without changing speed of movement and less frequent contact with novel object
Exp Paradigm: Open field test containing a novel object
 Open field test
 2 months
Social interaction1
Decreased
Description: Decreased social novelty indicated by no difference in contact between stranger and familiar mouse
Exp Paradigm: Three-chamber social interaction test
 Three-chamber social approach test
 2 months
Anxiety1
Increased
Description: Inreased anxiety demonstrated by less time spent in open arms and decreased open arm entries
Exp Paradigm: Elevated plus maze test
 Elevated plus maze test
 2 months
Maternal nurturing1
Decreased
Description: Cadps2 null female mice have poor maternal nurturing
Exp Paradigm: Neonate survival test
 Survival analysis: pups
 2 months
Gene expression1
Decreased
Description: Decreased expression with expressions limited to cell somas in layer V
Exp Paradigm: Cadps2 Expression
 Immunohistochemistry
 Unreported
Sleep pattern1
 No Change
 Home cage behavior
 2 months
Mortality/lethality1
 No Change
 General observations
 Unreported
Reproductive system development1
 No Change
 General observations
 Unreported
Anxiety1
 No Change
 Light-dark exploration test: crossing
 2 months
Spatial reference memory1
 No Change
 Y-maze test
 2 months
General locomotor activity1
 No Change
 Elevated plus maze test
 2 months
General locomotor activity1
 No Change
 Home cage behavior
 2 months
General locomotor activity1
 No Change
 Open field test
 2 months
Neuronal differentiation and specification in the brain1
 No Change
 
 P21
Neuronal differentiation and specification in the brain1
 No Change
 
 P7, P21
Neuronal number: Interneurons1
 No Change
 
 P17; P21
Olfaction1
 No Change
 Buried food test
 2 months
 Not Reported: Communications, Homeostasis, Immune response, Neurophysiology, Repetitive behavior, Seizure

M_CADPS2_5_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal differentiation and specification in the brain1
Decreased
Description: There is a transient decrease in the number of calbindin-positive interneurons in the hippocampus at P7 in Cadps2 het mice
 
 P7
Neuronal differentiation and specification in the brain1
Decreased
Description: Cadps2 het mice have reduced parvalbumin-positive interneurons in the neocortex
 
 P17; P21
Social interaction1
Decreased
Description: Decreased social interaction indicated by reduction in time spent approaching or interacting with stranger mouse cage
Exp Paradigm: open field test containing a stranger mouse
 Open field test
 2 months
Ultrasonic vocalization1
Decreased
Description: Decreased ultrasonic vocalizations indicated by reduced calls and call duration
Exp Paradigm: USV measurements of neonates
 Monitoring ultrasonic vocalizations: maternal separation
 P5-P10
Sleep pattern1
 No Change
 Home cage behavior
 2 months
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 2 months
Neuronal differentiation and specification in the brain1
 No Change
 
 P21
Neuronal differentiation and specification in the brain1
 No Change
 
 P7, P21
Neuronal number: Interneurons1
 No Change
 
 P17; P21
 Not Reported: Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neurophysiology, Repetitive behavior, Seizure, Sensory


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
BZRAP1 benzodiazapine receptor (peripheral) associated protein 1 9256 O95153 Y2H
Corominas R , et al. 2014
C19ORF45 Uncharacterized protein C19orf45 374877 Q8NA69 IP; LC-MS/MS
Huttlin EL , et al. 2015
DMD dystrophin 1756 P11532 Y2H; High-throughput fluorescence polarization interaction analysis assay
Y2H
Cisternas FA , et al. 2003
DRD2 dopamine receptor D2 1813 P14416 Y2H; IP/WB; High-throughput fluorescence polarization interaction analysis assay
Binda AV , et al. 2005
FMR1 fragile X mental retardation 1 2332 G8JLE9 PAR-CLIP
Ascano M Jr , et al. 2012
MEGF10 multiple EGF-like-domains 10 84466 Q96KG7 Y2H
Nakayama M , et al. 2002
UBE2D1 ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast) 7321 P51668 Y2H
van Wijk SJ , et al. 2009
UBE2D2 ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, yeast) 7322 P62837 Y2H
van Wijk SJ , et al. 2009
UBE2D3 ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast) 7323 P61077 Y2H
van Wijk SJ , et al. 2009
UBE2D4 Ubiquitin-conjugating enzyme E2 D4 51619 Q9Y2X8 Y2H
van Wijk SJ , et al. 2009
UBE2E1 ubiquitin-conjugating enzyme E2E 1 7324 P51965 Y2H
van Wijk SJ , et al. 2009
UBE2E3 ubiquitin-conjugating enzyme E2E 3 10477 Q969T4 Y2H
van Wijk SJ , et al. 2009
UBE2N ubiquitin-conjugating enzyme E2N 7334 P61088 Y2H
van Wijk SJ , et al. 2009
UBE2U Ubiquitin-conjugating enzyme E2 U 148581 Q5VVX9 Y2H
van Wijk SJ , et al. 2009
UBE2W ubiquitin-conjugating enzyme E2W (putative) 55284 Q96B02 Y2H
van Wijk SJ , et al. 2009
DMD dystrophin 1756 P11532 Y2H; High-throughput fluorescence polarization interaction analysis assay
Y2H
Cisternas FA , et al. 2003
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
BDNF brain-derived neurotrophic factor 24225 P23363 IP/WB
Sadakata T , et al. 2004

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